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Journal articles on the topic 'INKT cells'

Author: Grafiati

Published: 4 June 2021

Last updated: 18 September 2022

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1

Uddin, Mohammad Nizam, Dil Afroz Sultana, Kyle J. Lorentsen, et al. "Transcription factor Bcl11b sustains iNKT1 and iNKT2 cell programs, restricts iNKT17 cell program, and governs iNKT cell survival." Proceedings of the National Academy of Sciences 113, no. 27 (2016): 7608–13. http://dx.doi.org/10.1073/pnas.1521846113.

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Invariant natural killer T (iNKT) cells are innate-like T cells that recognize glycolipid antigens and play critical roles in regulation of immune responses. Based on expression of the transcription factors (TFs) Tbet, Plzf, and Rorγt, iNKT cells have been classified in effector subsets that emerge in the thymus, namely, iNKT1, iNKT2, and iNKT17. Deficiency in the TF Bcl11b in double-positive (DP) thymocytes has been shown to cause absence of iNKT cells in the thymus and periphery due to defective self glycolipid processing and presentation by DP thymocytes and undefined intrinsic alterations

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2

Maas-Bauer, Kristina, Juliane K. Lohmeyer, Toshihito Hirai, et al. "Invariant natural killer T-cell subsets have diverse graft-versus-host-disease–preventing and antitumor effects." Blood 138, no. 10 (2021): 858–70. http://dx.doi.org/10.1182/blood.2021010887.

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Abstract Invariant natural killer T (iNKT) cells are a T-cell subset with potent immunomodulatory properties. Experimental evidence in mice and observational studies in humans indicate that iNKT cells have antitumor potential as well as the ability to suppress acute and chronic graft-versus-host-disease (GVHD). Murine iNKT cells differentiate during thymic development into iNKT1, iNKT2, and iNKT17 sublineages, which differ transcriptomically and epigenomically and have subset-specific developmental requirements. Whether distinct iNKT sublineages also differ in their antitumor effect and their

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3

Maas-Bauer, Kristina, Federico Simonetta, Toshihito Hirai, et al. "Invariant Natural Killer T Cell Subsets Have Diverse Functions: iNKT2 and iNKT17 Protect from Graft-Versus-Host-Disease, Whereas iNKT1 Have Antitumor Potential." Blood 132, Supplement 1 (2018): 475. http://dx.doi.org/10.1182/blood-2018-99-113673.

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Abstract Invariant natural killer T (iNKT) cells are an interesting subpopulation of T cells that can potently inhibit graft-versus-host-disease (GVHD) through the production of Interleukin 4 (IL-4), while also carrying anti-tumor potential (Leveson-Gower et al. Blood. 2011;117:3220-9; Schneidawind et al. Blood. 2014;124:3320-8). Murine iNKT cells differentiate during thymic development into three distinct sublineages, named according to the classification of conventional T cells: Th1-like iNKT (iNKT1) cells, Th2-like iNKT (iNKT2) cells, and Th-17 like iNKT (iNKT17) cells (Brennan et al. Nat R

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4

Patel, Nishant P., Peng Guan, Devika Bahal, et al. "Cancer Immunotherapeutic Potential of NKTT320, a Novel, Invariant, Natural Killer T Cell-Activating, Humanized Monoclonal Antibody." International Journal of Molecular Sciences 21, no. 12 (2020): 4317. http://dx.doi.org/10.3390/ijms21124317.

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Invariant natural killer T cells (iNKTs) directly kill tumor cells and trans-activate the anti-tumor functions of dendritic cells (DC), natural killer (NK) cells, and T and B cells. As such, iNKTs serve as a powerful tool for use in cell-based cancer immunotherapy. iNKT cell activation commonly requires engagement of the invariant T cell receptor (iTCR) by CD1d presenting glycolipid antigens. However, transformed cells often down-regulate CD1d expression, which results in a reduction of iNKT cell anti-tumor functions. One approach to circumvent this critical barrier to iNKT cell activation is

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5

Chen, Dongzhi, Wenbin Xu, Jingfang Teng, et al. "Migration, Distribution, and Safety Evaluation of Specific Phenotypic and Functional Mouse Spleen-Derived Invariant Natural Killer T2 Cells after Adoptive Infusion." Mediators of Inflammation 2021 (December 8, 2021): 1–11. http://dx.doi.org/10.1155/2021/5170123.

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Herein, the migration distribution and safety of specific phenotypic and functionally identified spleen-derived invariant natural killer T2 (iNKT2) cells after adoptive infusion in mice were studied. The proliferation and differentiation of iNKT cells were induced by intraperitoneal injection of α-galactosylceramide (α-GalCer) in vivo. Mouse spleens were isolated in a sterile environment. iNKT cells were isolated by magnetic-activated cell sorting columns (MS columns). Cytometric bead array (CBA) assay was used to detect cytokine secretion in the supernatant stimulated by iNKT cells. The basic

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6

Jahnke, Simona, Hannes Schmid, Kathy-Ann Secker, et al. "Invariant Natural Killer T Cells from Donor Lymphocyte Infusions (DLI-iNKTs) Contribute to Anti-Tumor Immunity after Allogeneic Hematopoietic Cell Transplantation." Blood 132, Supplement 1 (2018): 3340. http://dx.doi.org/10.1182/blood-2018-99-111745.

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Abstract Allogeneic hematopoietic cell transplantation (HCT) is a curative treatment option for hematologic malignancies but relapse remains the most common cause of death. Infusion of donor lymphocytes (DLIs) can induce remission and prolong survival by exerting potent graft-versus-leukemia (GVL) effects. However, sufficient tumor control cannot be established in all patients. We showed previously that invariant natural killer T (iNKT) cells promote anti-tumor immunity in murine models of allogeneic HCT without exacerbating graft-versus-host disease (GVHD). We therefore studied iNKT cells in

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7

Castillo, Eliseo F., Luis F. Acero, Spencer W. Stonier, Dapeng Zhou, and Kimberly S. Schluns. "Thymic and peripheral microenvironments differentially mediate development and maturation of iNKT cells by IL-15 transpresentation." Blood 116, no. 14 (2010): 2494–503. http://dx.doi.org/10.1182/blood-2010-03-277103.

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Abstract Invariant NKT (iNKT) cells are an innate type of T cells, which respond rapidly on activation. iNKT cells acquire these innate-like abilities during development; however, the signals driving development and functional maturation remain only partially understood. Because interleukin-15 (IL-15) is crucial for iNKT development and is delivered by transpresentation, we set out to identify the cell types providing IL-15 to developing iNKT cells and determine their role at the various states of development and maturation. We report here that transpresentation of IL-15 by parenchymal cells w

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8

Kanda, Masatoshi, Hiroyuki Yamanaka, Satoshi Kojo та ін. "Transcriptional regulator Bhlhe40 works as a cofactor of T-bet in the regulation of IFN-γ production in iNKT cells". Proceedings of the National Academy of Sciences 113, № 24 (2016): E3394—E3402. http://dx.doi.org/10.1073/pnas.1604178113.

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Invariant natural killer T (iNKT) cells are a subset of innate-like T cells that act as important mediators of immune responses. In particular, iNKT cells have the ability to immediately produce large amounts of IFN-γ upon activation and thus initiate immune responses in various pathological conditions. However, molecular mechanisms that control IFN-γ production in iNKT cells are not fully understood. Here, we report that basic helix–loop–helix transcription factor family, member e40 (Bhlhe40), is an important regulator for IFN-γ production in iNKT cells. Bhlhe40 is highly expressed in stage 3

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9

Purbhoo, Marco, Burcu Yigit, Darrian Moskowitz, et al. "400 Persistence and tissue distribution of agent-797 – a native allogeneic iNKT cell-therapy drug product." Journal for ImmunoTherapy of Cancer 9, Suppl 2 (2021): A432. http://dx.doi.org/10.1136/jitc-2021-sitc2021.400.

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BackgroundInvariant Natural Killer T (iNKT) cells are key effectors and regulators of immune responses, making them an ideal immunotherapy. There is a paucity of evidence describing the persistence and trafficking of these cells in humans to inform the optimal clinical application. Here, we describe the development of a murine Xenograft model for the study of an unmodified human iNKT cell therapy (Agent-797) and present data on the persistence and tissue distribution of human iNKT cells in this model. We further describe the development and validation of a digital PCR-based methodology to trac

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10

Metelitsa, Leonid S., Hong-Wei Wu, Hong Wang, et al. "Natural Killer T Cells Infiltrate Neuroblastomas Expressing the Chemokine CCL2." Journal of Experimental Medicine 199, no. 9 (2004): 1213–21. http://dx.doi.org/10.1084/jem.20031462.

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CD1d-restricted Vα24-Jα18–invariant natural killer T cells (iNKTs) are potentially important in tumor immunity. However, little is known about their localization to tumors. We analyzed 98 untreated primary neuroblastomas from patients with metastatic disease (stage 4) for tumor-infiltrating iNKTs using TaqMan® reverse transcription polymerase chain reaction and immunofluorescent microscopy. 52 tumors (53%) contained iNKTs, and oligonucleotide microarray analysis of the iNKT+ and iNKT− tumors revealed that the former expressed higher levels of CCL2/MCP-1, CXCL12/SDF-1, CCL5/RANTES, and CCL21/SL

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11

Smith, Drake J., Siyuan Liu, Sunjong Ji, et al. "Genetic engineering of hematopoietic stem cells to generate invariant natural killer T cells." Proceedings of the National Academy of Sciences 112, no. 5 (2015): 1523–28. http://dx.doi.org/10.1073/pnas.1424877112.

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Invariant natural killer T (iNKT) cells comprise a small population of αβ T lymphocytes. They bridge the innate and adaptive immune systems and mediate strong and rapid responses to many diseases, including cancer, infections, allergies, and autoimmunity. However, the study of iNKT cell biology and the therapeutic applications of these cells are greatly limited by their small numbers in vivo (∼0.01–1% in mouse and human blood). Here, we report a new method to generate large numbers of iNKT cells in mice through T-cell receptor (TCR) gene engineering of hematopoietic stem cells (HSCs). We showe

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12

Dempsey, Laurie A. "Limiting iNKT cells." Nature Immunology 15, no. 3 (2014): 222. http://dx.doi.org/10.1038/ni.2839.

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13

He, Qing, Linlin Liu, Qiaoyu Yang, et al. "Invariant natural killer T cells promote immunogenic maturation of lung dendritic cells in mouse models of asthma." American Journal of Physiology-Lung Cellular and Molecular Physiology 313, no. 6 (2017): L973—L990. http://dx.doi.org/10.1152/ajplung.00340.2016.

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Our previous study showed that invariant natural killer T (iNKT) cells might act as an adjuvant to promote Th2 inflammatory responses in an OVA-induced mouse model of allergic asthma, but the mechanism remains unknown. To clarify the underlying mechanism through which iNKT cells promote Th2 inflammatory responses, we investigated the modulatory influence of iNKT cells on phenotypic and functional maturation of lung dendritic cells (LDCs) using iNKT cell-knockout mice, specific iNKT cell activation, coculture experiments, and adoptive transfer of iNKT cells in mouse models of asthma. Our data s

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14

Wermeling, Fredrik, Sara M. Lind, Emilie Domange Jordö, Susanna L. Cardell, and Mikael C. I. Karlsson. "Invariant NKT cells limit activation of autoreactive CD1d-positive B cells." Journal of Experimental Medicine 207, no. 5 (2010): 943–52. http://dx.doi.org/10.1084/jem.20091314.

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Faulty activation of autoreactive B cells is a hallmark of autoimmune diseases like systemic lupus erythematosus (SLE). An important feature restricting activation of autoreactive B cells is efficient removal of apoptotic material. Mounting evidence also connects a primary defect in invariant natural killer T (iNKT) cells to autoimmune disease development. However, exactly how this unconventional T cell subset is involved remains to be defined. Here, we identify a suppressive role for iNKT cells in a model where autoantibody production is triggered by an increased load of circulating apoptotic

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15

Qin, Yingyu, Sejin Oh, Sojung Lim, Jung Hoon Shin, Min Sang Yoon, and Se-Ho Park. "Invariant NKT cells facilitate cytotoxic T-cell activation via direct recognition of CD1d on T cells." Experimental & Molecular Medicine 51, no. 10 (2019): 1–9. http://dx.doi.org/10.1038/s12276-019-0329-9.

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Abstract Invariant natural killer T (iNKT) cells are a major subset of NKT cells that recognize foreign and endogenous lipid antigens presented by CD1d. Although iNKT cells are characteristically autoreactive to self-antigens, the role of iNKT cells in the regulation of cytotoxic T lymphocytes (CTL) has been elucidated using α-galactosylceramide (α-GalCer), a strong synthetic glycolipid that is presented by professional antigen presenting cells (APCs), such as dendritic cells. Despite the well-known effects of α-GalCer and dendritic cells on lipid antigen presentation, the physiological role o

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16

Vomhof-DeKrey, Emilie E., Jennifer Yates, Thomas Hägglöf, et al. "Cognate interaction with iNKT cells expands IL-10–producing B regulatory cells." Proceedings of the National Academy of Sciences 112, no. 40 (2015): 12474–79. http://dx.doi.org/10.1073/pnas.1504790112.

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Successful induction of B-cell activation and memory depends on help from CD4+ T cells. Invariant natural killer T (iNKT) cells (glycolipid-specific, CD1d-restricted innate lymphocytes) provide both cognate (direct) and noncognate (indirect) helper signals to enhance B-cell responses. Both forms of iNKT-cell help induce primary humoral immune responses, but only noncognate iNKT-cell help drives humoral memory and plasma cells. Here, we show that iNKT cognate help for B cells is fundamentally different from the help provided by conventional CD4+ T cells. Cognate iNKT-cell help drives an early,

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17

Milpied, Pierre, Bérangère Massot, Amédée Renand, et al. "IL-17–producing invariant NKT cells in lymphoid organs are recent thymic emigrants identified by neuropilin-1 expression." Blood 118, no. 11 (2011): 2993–3002. http://dx.doi.org/10.1182/blood-2011-01-329268.

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Abstract Despite increasing knowledge on the mechanisms of invariant natural killer T (iNKT)–cell development in the thymus, the function of recent thymic emigrant (RTE) iNKT cells remains largely unexplored, principally because of a lack of bona fide markers to distinguish RTE from long-lived iNKT cells. Whether the recently described IL-17–producing iNKT cell subset is part of RTE has notably not been addressed. In the present study, we show that neuropilin-1 (Nrp-1), a transmembrane receptor mainly found on T-regulatory (Treg) cells in the murine immune system, is specifically expressed on

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Yamaura, Ayako, Chie Hotta, Masatoshi Nakazawa, Luc Van Kaer та Mutsuhiko Minami. "Human invariant Vα24+ natural killer T cells acquire regulatory functions by interacting with IL-10–treated dendritic cells". Blood 111, № 8 (2008): 4254–63. http://dx.doi.org/10.1182/blood-2007-04-085142.

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Abstract Glycolipid-reactive Vα24+ invariant natural killer T (iNKT) cells have been implicated in regulating a variety of immune responses and in the induction of immunologic tolerance. Activation of iNKT cells requires interaction with professional antigen-presenting cells, such as dendritic cells (DCs). We have investigated the capacity of distinct DC subsets to modulate iNKT cell functions. We demonstrate that tolerogenic DCs (tolDCs), generated by treatment of monocyte-derived DC with interleukin (IL)-10, induced regulatory functions in human iNKT cells. tolDCs, compared with immunogenic

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19

Torreno-Pina, Juan A., Carlo Manzo, Mariolina Salio, et al. "The actin cytoskeleton modulates the activation of iNKT cells by segregating CD1d nanoclusters on antigen-presenting cells." Proceedings of the National Academy of Sciences 113, no. 6 (2016): E772—E781. http://dx.doi.org/10.1073/pnas.1514530113.

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Invariant natural killer T (iNKT) cells recognize endogenous and exogenous lipid antigens presented in the context of CD1d molecules. The ability of iNKT cells to recognize endogenous antigens represents a distinct immune recognition strategy, which underscores the constitutive memory phenotype of iNKT cells and their activation during inflammatory conditions. However, the mechanisms regulating such “tonic” activation of iNKT cells remain unclear. Here, we show that the spatiotemporal distribution of CD1d molecules on the surface of antigen-presenting cells (APCs) modulates activation of iNKT

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Loureiro, J. Pedro, Mariana S. Cruz, Ana P. Cardoso, Maria J. Oliveira, and M. Fátima Macedo. "Human iNKT Cells Modulate Macrophage Survival and Phenotype." Biomedicines 10, no. 7 (2022): 1723. http://dx.doi.org/10.3390/biomedicines10071723.

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CD1d-restricted invariant Natural Killer T (iNKT) cells are unconventional innate-like T cells whose functions highly depend on the interactions they establish with other immune cells. Although extensive studies have been reported on the communication between iNKT cells and macrophages in mice, less data is available regarding the relevance of this crosstalk in humans. Here, we dove into the human macrophage-iNKT cell axis by exploring how iNKT cells impact the survival and polarization of pro-inflammatory M1-like and anti-inflammatory M2-like monocyte-derived macrophages. By performing in vit

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Song, Weihua, Hans J. J. van der Vliet, Ruojie Wang, et al. "In Vitro Generation of Highly-Purified Functional Invariant NKT Cells: A Strategy for Immunotherapy in Multiple Myeloma." Blood 106, no. 11 (2005): 5183. http://dx.doi.org/10.1182/blood.v106.11.5183.5183.

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Abstract Invariant NKT (iNKT) cells are characterized by the expression of invariant T-cell receptor encoded by Vα24-JαQ and NK receptors. iNKT cells recognize glycolipid antigens with CD1d restriction, and play an important immunoregulatory role in innate immunity. Through the production of IFN-γ, iNKT cells can contribute to immune surveillance in malignancy. However, in progressive multiple myeloma (MM), as well as in other advanced cancers, iNKT cells have a marked deficiency of ligand-dependent IFN-γ production. Thus, the development of effective iNKT cells is a novel strategy for the imm

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22

Malard, Florent, Myriam Labopin, Patrice Chevallier, et al. "Larger number of invariant natural killer T cells in PBSC allografts correlates with improved GVHD-free and progression-free survival." Blood 127, no. 14 (2016): 1828–35. http://dx.doi.org/10.1182/blood-2015-12-688739.

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Abstract We studied the impact of a set of immune cells contained within granulocyte colony-stimulating factor–mobilized peripheral blood stem cell grafts (naïve and memory T-cell subsets, B cells, regulatory T cells, invariant natural killer T cells [iNKTs], NK cells, and dendritic cell subsets) in patients (n = 80) undergoing allogeneic stem cell transplantation (SCT), using the composite end point of graft-versus-host disease (GVHD)-free and progression-free survival (GPFS) as the primary end point. We observed that GPFS incidences in patients receiving iNKT doses above and below the median

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Park, Hyun Jung, Sung Won Lee, Luc Van Kaer та Seokmann Hong. "CD1d-Dependent iNKT Cells Control DSS-Induced Colitis in a Mouse Model of IFNγ-Mediated Hyperinflammation by Increasing IL22-Secreting ILC3 Cells". International Journal of Molecular Sciences 22, № 3 (2021): 1250. http://dx.doi.org/10.3390/ijms22031250.

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We have previously shown that CD1d-restricted iNKT cells suppress dysregulated IFNγ expression and intestinal inflammation in Yeti mice on the C57BL/6 background. Since type 3 innate lymphoid cells (ILC3s) in mesenteric lymph nodes (MLN) protect against intestinal inflammation in a CD1d-associated manner, we investigated whether crosstalk between iNKT cells and MLN ILC3s controls IFNγ-mediated intestinal inflammation in Yeti mice. We found that Yeti mice display increased levels of ILC3s and that iNKT cell deficiency in Yeti/CD1d KO mice decreases levels of IL22-producing ILC3s during DSS-indu

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Brigl, Manfred, Raju V. V. Tatituri, Gerald F. M. Watts, et al. "Innate and cytokine-driven signals, rather than microbial antigens, dominate in natural killer T cell activation during microbial infection." Journal of Experimental Medicine 208, no. 6 (2011): 1163–77. http://dx.doi.org/10.1084/jem.20102555.

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Invariant natural killer T cells (iNKT cells) are critical for host defense against a variety of microbial pathogens. However, the central question of how iNKT cells are activated by microbes has not been fully explained. The example of adaptive MHC-restricted T cells, studies using synthetic pharmacological α-galactosylceramides, and the recent discovery of microbial iNKT cell ligands have all suggested that recognition of foreign lipid antigens is the main driver for iNKT cell activation during infection. However, when we compared the role of microbial antigens versus innate cytokine-driven

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Moreno, María, Berber M. Mol, Silvia von Mensdorff-Pouilly, et al. "Differential indirect activation of human invariant natural killer T cells by Toll-like receptor agonists." Immunotherapy 1, no. 4 (2009): 557–70. http://dx.doi.org/10.2217/imt.09.30.

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Aim: Invariant natural killer (iNK) T cells are activated by bacterial glycosphingolipids presented by CD1d on dendritic cells (DCs). Here, it was investigated whether Toll-like receptor (TLR) ligands derived from various microorganisms can either directly or indirectly (through DC activation) activate iNKT cells. Materials & Methods: TLR expression by iNKT cells was examined and the ability of various TLR ligands to activate iNKT cells was evaluated. Results: Although human iNKT cells express all TLRs, apart from TLR8, they did not respond directly to TLR ligands. However, iNKT cells beca

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Aoki, Takahiro, Mariko Takami, Tomozumi Takatani, et al. "Invariant NKT Cells Recognize Leukemia Cells with T-Cell and NK Receptors in a CD1d-Independent Manner." Blood 134, Supplement_1 (2019): 3225. http://dx.doi.org/10.1182/blood-2019-121817.

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Background: Invariant natural killer T (iNKT) cells are known as CD1d-restricted T cells that express the invariant T-cell receptors (TCR) Vα24 and Vβ11 in humans and specifically recognize glycolipid antigens such as α-galactosylceramide (αGalCer) presented by CD1d. iNKT cells show direct cytotoxicity toward CD1d-positive tumor cells presenting glycolipid antigens and indirect cytotoxicity by activating other cytotoxic immune cells or regulating CD1d-positive immunosuppressive cells in the tumor microenvironment. Although we previously reported that αGalCer-activated NKT cells exert a potent

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Mallevaey, Thierry, Josette Fontaine, Laetitia Breuilh, et al. "Invariant and Noninvariant Natural Killer T Cells Exert Opposite Regulatory Functions on the Immune Response during Murine Schistosomiasis." Infection and Immunity 75, no. 5 (2007): 2171–80. http://dx.doi.org/10.1128/iai.01178-06.

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ABSTRACT CD1d-restricted natural killer T (NKT) cells represent a heterogeneous population of innate memory immune cells expressing both NK and T-cell markers distributed into two major subsets, i.e., invariant NKT (iNKT) cells, which express exclusively an invariant T-cell receptor (TCR) α chain (Vα14Jα18 in mice), and non-iNKT cells, which express more diverse TCRs. NKT cells quickly produce Th1- and/or Th2-type cytokines following stimulation with glycolipid antigen (Ag) and, through this property, play potent immunoregulatory roles in autoimmune diseases, cancer, and infection. No study ha

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Foley, J. F. "iNKT Cells Reduce Obesity." Science Signaling 5, no. 243 (2012): ec249-ec249. http://dx.doi.org/10.1126/scisignal.2003632.

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MIYAKE, Sachiko. "Immunoregulation by iNKT Cells." YAKUGAKU ZASSHI 129, no. 6 (2009): 649–53. http://dx.doi.org/10.1248/yakushi.129.649.

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Bedard, Melissa, Dilip Shrestha, David A. Priestman, et al. "Sterile activation of invariant natural killer T cells by ER-stressed antigen-presenting cells." Proceedings of the National Academy of Sciences 116, no. 47 (2019): 23671–81. http://dx.doi.org/10.1073/pnas.1910097116.

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Invariant NKT (iNKT) cells have the unique ability to shape immunity during antitumor immune responses and other forms of sterile and nonsterile inflammation. Recent studies have highlighted a variety of classes of endogenous and pathogen-derived lipid antigens that can trigger iNKT cell activation under sterile and nonsterile conditions. However, the context and mechanisms that drive the presentation of self-lipid antigens in sterile inflammation remain unclear. Here we report that endoplasmic reticulum (ER)-stressed myeloid cells, via signaling events modulated by the protein kinase RNA-like

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Scheuplein, Felix, Abraham Thariath, Robert Mashal, and Robert Schaub. "Mouse Invariant TCR Specific Monoclonal Antibody NKT14: A Novel Tool To Manipulate Invariant NKT Cell Function In Vivo." Blood 122, no. 21 (2013): 3478. http://dx.doi.org/10.1182/blood.v122.21.3478.3478.

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Abstract The iNKT cell represents a novel therapeutic target for important hematologic diseases such as sickle cell disease (SCD) and myeloma. While an antibody specifically targeting human iNKT cells is now in a clinical trial, no surrogate reagent that specifically recognizes murine iNKT cells has been previously reported. This abstract defines work on a unique, recently developed antibody specifically directed to the T cell receptor of the mouse iNKT cell. These cells are a small subset of T lymphocytes that share characteristics with adaptive as well as innate immune cells. In contrast to

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Hsu, Chien-Ya, Yu-Shan Chueh, Ming-Ling Kuo, et al. "Expansion of invariant natural killer T cells from systemic lupus erythematosus patients by alpha-Galactosylceramide and IL-15." PLOS ONE 16, no. 12 (2021): e0261727. http://dx.doi.org/10.1371/journal.pone.0261727.

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CD1d-restricted invariant natural killer T cells (iNKT cells) may play an important role in the pathogenesis of systemic lupus erythematosus (SLE). Interleukin (IL)-15 is a pro-inflammatory cytokine which is over-expressed in SLE patients. In the present study, we investigated the iNKT cell expansion of mononuclear cells (MNCs) from SLE patients following 10 days’ culture with α-galactosylceramide (α-Galcer) and /or IL-15. We sought to determine the phenotypic and functional characteristics of the expanded iNKT cells compared to healthy controls and correlated with disease activity. We observe

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Mavers, Melissa, Derek Hollingsworth, Chaiyaporn Boonchalermvichian, et al. "Engineering Human Invariant Natural Killer T (iNKT) Cells to Overexpress Immunomodulatory Cytokines." Blood 138, Supplement 1 (2021): 3888. http://dx.doi.org/10.1182/blood-2021-153975.

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Abstract Many studies have shown the important role that invariant natural killer T (iNKT) cells play in suppression of graft-versus-host disease (GVHD). Murine studies have also demonstrated multiple subsets of iNKT cells, including those with pro-inflammatory and immunosuppressive properties. The prevention of murine acute GVHD by the adoptive transfer of immunomodulatory iNKT cells suggests that this approach would be ideal for clinical translation. However, the heterogeneity of human iNKT cells remains poorly understood, and the uncertain ability to identify immunosuppressive human iNKT ce

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Chuang, Ya-Ting, Wan-Chu Chuang, Chih-Chun Liu та ін. "Ets1 Promotes the Differentiation of Post-Selected iNKT Cells through Regulation of the Expression of Vα14Jα18 T Cell Receptor and PLZF". International Journal of Molecular Sciences 22, № 22 (2021): 12199. http://dx.doi.org/10.3390/ijms222212199.

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The transcription factor Ets1 is essential for the development/differentiation of invariant Natural Killer T (iNKT) cells at multiple stages. However, its mechanisms of action and target genes in iNKT cells are still elusive. Here, we show that Ets1 is required for the optimal expression of the Vα14Jα18 T cell receptor (TCR) in post-selected thymic iNKT cells and their immediate differentiation. Ets1 is also critical for maintaining the peripheral homeostasis of iNKT cells, which is a role independent of the expression of the Vα14Jα18 TCR. Genome-wide transcriptomic analyses of post-selected i

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Imataki, Osamu, Makito Tanaka, Alla Berezovskaya, Marcus O. Butler, Lee M. Nadler та Naoto Hirano. "Endogenous Ligands Selectively Stimulate Highly Avid Autoreactive Human Invariant Natural Killer T Cells with Distinctive T-Cell Receptor Vβ11 CDR3 Sequence Motifs". Blood 118, № 21 (2011): 999. http://dx.doi.org/10.1182/blood.v118.21.999.999.

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Abstract Abstract 999 Human CD1d-restricted invariant natural killer T (iNKT) cells are a unique subset of innate T-cells that carry an invariant T-cell receptor (TCR) Vα24 chain paired with a TCR Vβ11 chain. They constitutively express a variety of activation and memory markers and possess the capacity to rapidly produce a variety of cytokines including IFN-γ and IL-4 upon TCR engagement. As an immune response launches, iNKT cells can induce innate immune responses and serve as a bridge between innate and adaptive immunity. In addition, it has also been shown that iNKT cells themselves have a

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Sedimbi, Saikiran K., Thomas Hägglöf, Manasa G. Garimella, et al. "Combined proinflammatory cytokine and cognate activation of invariant natural killer T cells enhances anti-DNA antibody responses." Proceedings of the National Academy of Sciences 117, no. 16 (2020): 9054–63. http://dx.doi.org/10.1073/pnas.1920463117.

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Invariant natural killer T (iNKT) cells serve as early rapid responders in the innate immune response to self-derived autoantigens and pathogen-derived danger signals and antigens. iNKT cells can serve both as helpers for effector B cells and negatively regulate autoreactive B cells. Specifically, iNKT cells drive B cell proliferation, class switch, and antibody production to induce primary antigen-specific immune responses. On the other hand, inflammasome-mediated activation drives accumulation of neutrophils, which license iNKT cells to negatively regulate autoreactive B cells via Fas ligand

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Spanoudakis, Emmanouil, Menelaos Papoutselis, Ioannis Kotsianidis, et al. "Over-Expression of RANKL In Invariant NKT Cells Is Characteristic of Active Myeloma but Not of MGUS or Asymptomatic Myeloma." Blood 116, no. 21 (2010): 4049. http://dx.doi.org/10.1182/blood.v116.21.4049.4049.

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Abstract Abstract 4049 RANKL upregulation in the multiple myeloma (MM) microenvironment and in particular in malignant plasma cells, osteoblasts and T-cells is pivotal for the pathological activation of osteoclasts and development of bone disease in multiple myeloma. Invariant NKT cells (iNKT) is a small but powerful subset of CD1d-restricted, glycolipid-specific immunoregulatory T-cells. iNKT cells are dysfunctional in MM in that they display reduced ability to secrete interferon-gamma contributing thus to myeloma immune evasion. Whether iNKT cells also contribute to the enhanced RANKL produc

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Yang, Jun-Qi, Yonghua Zhou, and Ram Raj Singh. "Effects of Invariant NKT Cells on Parasite Infections and Hygiene Hypothesis." Journal of Immunology Research 2016 (2016): 1–9. http://dx.doi.org/10.1155/2016/2395645.

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Invariant natural killer T (iNKT) cells are unique subset of innate-like T cells recognizing glycolipids. iNKT cells can rapidly produce copious amounts of cytokines upon antigen stimulation and exert potent immunomodulatory activities for a wide variety of immune responses and diseases. We have revealed the regulatory effect of iNKT cells on autoimmunity with a serial of publications. On the other hand, the role of iNKT cells in parasitic infections, especially in recently attractive topic “hygiene hypothesis,” has not been clearly defined yet. Bacterial and parasitic cell wall is a cellular

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Fedeli, Maya, Michela Riba, Jose Manuel Garcia Manteiga та ін. "miR-17∼92 family clusters control iNKT cell ontogenesis via modulation of TGF-β signaling". Proceedings of the National Academy of Sciences 113, № 51 (2016): E8286—E8295. http://dx.doi.org/10.1073/pnas.1612024114.

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Invariant natural killer T cells (iNKT) cells are T lymphocytes displaying innate effector functions, acquired through a distinct thymic developmental program regulated by microRNAs (miRNAs). Deleting miRNAs by Dicer ablation (Dicer KO) in thymocytes selectively impairs iNKT cell survival and functional differentiation. To unravel this miRNA-dependent program, we systemically identified transcripts that were differentially expressed between WT and Dicer KO iNKT cells at different differentiation stages and predicted to be targeted by the iNKT cell-specific miRNAs. TGF-β receptor II (TGF-βRII),

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Yu, Jennifer C., Gene W. Lin, Jenny Kim, and Joel Linden. "Activated Human iNKT Cells in Pediatric Sickle Cell Disease Patients and in Culture Upregulate Ectonucleotidase CD39 and Adenosine a2A Receptor." Blood 124, no. 21 (2014): 2734. http://dx.doi.org/10.1182/blood.v124.21.2734.2734.

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Abstract Background: Sickle cell disease (SCD) is a chronic degenerative disease punctuated by periodic painful vaso-occlusive crises (pVOC). When sickle hemoglobin polymerizes, it causes erythrocytes to become rigid and sticky and produces multi-cellular aggregates that can occlude venules. We have shown that invariant natural killer T (iNKT) cells are pivotal in causing inflammation and injury in sickle cell disease (Wallace KL, Marshall MA, et al. Blood. 2009; 114(3):667-76). Activation of iNKT cells causes an induction of anti-inflammatory adenosine A2A receptors (A2ARs) that have a negati

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Li, Yan-Ruide, Yang Zhou, Matthew Wilson та ін. "Tumor-Localized Administration of α-GalCer to Recruit Invariant Natural Killer T Cells and Enhance Their Antitumor Activity against Solid Tumors". International Journal of Molecular Sciences 23, № 14 (2022): 7547. http://dx.doi.org/10.3390/ijms23147547.

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Invariant natural killer T (iNKT) cells have the capacity to mount potent anti-tumor reactivity and have therefore become a focus in the development of cell-based immunotherapy. iNKT cells attack tumor cells using multiple mechanisms with a high efficacy; however, their clinical application has been limited because of their low numbers in cancer patients and difficulties in infiltrating solid tumors. In this study, we aimed to overcome these critical limitations by using α-GalCer, a synthetic glycolipid ligand specifically activating iNKT cells, to recruit iNKT to solid tumors. By adoptively t

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Du, Jing, Katelyn Paz, Govindarajan Thangavelu, et al. "Invariant natural killer T cells ameliorate murine chronic GVHD by expanding donor regulatory T cells." Blood 129, no. 23 (2017): 3121–25. http://dx.doi.org/10.1182/blood-2016-11-752444.

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Schneidawind, Dominik, Jeanette Baker, Corina Buechele, Everett H. Meyer, and Robert S. Negrin. "Third Party Invariant Natural Killer T Cells Protect from Graft-Versus-Host Disease Lethality through Expansion of Donor CD4+FoxP3+ Regulatory T Cells." Blood 124, no. 21 (2014): 3825. http://dx.doi.org/10.1182/blood.v124.21.3825.3825.

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Abstract Graft-versus-host disease (GVHD) is driven by extensive activation and proliferation of alloreactive donor T cells causing significant morbidity and mortality following allogeneic hematopoietic cell transplantation (HCT). Invariant natural killer T (iNKT) cells are potent regulators of immune responses in both humans (TCRα Vα24-Jα18) and mice (TCRα Vα14-Jα18). As the iNKT cell receptor and the glycolipid-presenting molecule CD1d interaction is highly conserved, we explored the role of adoptively transferred third party CD4+ iNKT cells in a murine model of allogeneic HCT. BALB/c (H-2Kd

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Strong, Beverly SI, Tess J. Newkold, Amanda E. Lee, Lucas E. Turner, Jonathon W. Heusel, and Aimen F. Shaaban. "Asymmetric Allospecific Signals Shape iNKT Cell Lineage Fate Decisions." Blood 126, no. 23 (2015): 4274. http://dx.doi.org/10.1182/blood.v126.23.4274.4274.

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Abstract Invariant NKT (iNKT) cells are glycolipid-reactive alpha/beta T cells which have an important role in the regulation of GVHD after allogeneic bone marrow transplantation. During thymic development, murine iNKT cells divide into three transcriptionally distinct lineages-NKT1, NKT2, and NKT17 that differ in their cytokine expression profile both at rest and upon antigen recognition via their TCR. Given that the lineage profile of iNKT cells varies dramatically between inbred strains of mice, it has been postulated that recognition of allospecific glycolipids determines iNKT cell lineage

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Thedrez, Aurelie, Claudia de Lalla, Sophie Allain, et al. "CD4 engagement by CD1d potentiates activation of CD4+ invariant NKT cells." Blood 110, no. 1 (2007): 251–58. http://dx.doi.org/10.1182/blood-2007-01-066217.

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The CD4 coreceptor is crucial in the activation of major histocompatibility complex (MHC) class II restricted CD4 + T lymphocytes by binding the same MHC class as the T-cell receptor (TCR) and by potentiating TCR-dependent signaling. CD4 is also expressed by invariant natural killer T cells (iNKT), which recognize natural and synthetic lipid antigens, such as α-galactosyl ceramide (α-GalCer), in association with the MHC class I–like CD1d molecule. Human iNKT cells can be divided into 2 major subsets depending on CD4 expression: CD4 + iNKT preferentially produce T-helper (Th)0/Th2 cytokines, wh

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Havenar-Daughton, Colin, Shamin Li, Kamel Benlagha та Julien C. Marie. "Development and function of murine RORγt+ iNKT cells are under TGF-β signaling control". Blood 119, № 15 (2012): 3486–94. http://dx.doi.org/10.1182/blood-2012-01-401604.

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Invariant natural killer T (iNKT) cells have the ability to rapidly secret cytokines in response to diverse stimuli, and therefore influence numerous immune reactions. Although IFN-γ and IL-4 are thought to dominate iNKT cytokine production, a distinct subset of iNKT cells, expressing RORγt and producing IL-17, has now been identified in both mice and humans. Although a role in pathogen and allergic responses has been assigned to the RORγt+ iNKT subset, factors controlling their development and function remain illusive. Here, we demonstrate that RORγt+ iNKT-cell differentiation obeys transform

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Linden, Joel, Gene Lin, Jennifer C. Yu, Donna S. Neuberg, David G. Nathan та Joshua J. Field. "NF-κB Activation Mediates Induction Of Anti-Inflammatory Adenosine A2A Receptors In iNKT Cells Of Sickle Cell Patients During Vaso-Occlusive Episodes and Upon Activation Of Cultured Human iNKT Cells". Blood 122, № 21 (2013): 975. http://dx.doi.org/10.1182/blood.v122.21.975.975.

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Abstract iNKT cells are activated in mice and people with vaso-occlusive sickle cell disease (SCD) and play a pivotal role in initiating an inflammatory cascade. In mice, iNKT cell activation requires NF-κB signaling [Stanic, AK et al. J Immunol. 172:4667, 2004]. In mice with SCD, lung inflammation is associated with induction in iNKT cells of IFN-γ and anti-inflammatory adenosine A2A receptor (A2AR) mRNAs [Wallace, KL et al. Blood 116:5010, 2010]. The A2AR is one of four G protein coupled adenosine receptors (A1, A2A, A2B and A3) and it is the most abundant adenosine receptor expressed in T c

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Schneidawind, Dominik, Antonio Pierini, Maite Alvarez, et al. "CD4+ Invariant Natural Killer T Cells Require NKG2D To Protect From Lethal Acute Graft-Versus-Host Disease." Blood 122, no. 21 (2013): 898. http://dx.doi.org/10.1182/blood.v122.21.898.898.

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Abstract Invariant Natural Killer T (iNKT) cells are a rare cell population in humans (TCRα Vα24-Jα18) and mice (TCRα Vα14-Jα18) that are characterized by a rapid release of immunoregulatory cytokines upon stimulation. The tolerogenic impact of host iNKT cells on graft-versus-host disease (GVHD) after conditioning with total lymphoid irradiation and anti-thymocyte globulin (TLI/ATG) has been shown previously (Lan et al., BBMT 2003). Moreover, we recently described a subset of CD49b+ NKT cells overlapping with iNKT cells and providing protection from acute GVHD mainly via an IL-4-dependent mech

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Yigit, Burcu, Darrian Moskowitz, Xavier Michelet, Antoine Tanne, and Marc Van Dijk. "205 AgenT-797, a native allogeneic ‘off-the-shelf’ iNKT cell therapy product shows anti-tumor activity in preclinical xenograft models." Journal for ImmunoTherapy of Cancer 9, Suppl 2 (2021): A216. http://dx.doi.org/10.1136/jitc-2021-sitc2021.205.

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BackgroundagenT-797 is an allogeneic, native invariant natural killer T (iNKT) cell therapy product currently in phase I clinical trials for cancer (heme and solid). iNKT cells are a distinct population of T cells that can recognize tumors via direct recognition of CD1d (an MHC-I like molecule presenting glycolipids) through the TCR or recognition of NK cell receptor ligands via various NK receptors. We developed agenT-797 from isolated and ex-vivo expanded peripheral blood iNKT cells. Here we describe in vivo xenograft models to demonstrate the overall tissue distribution, tumor infiltration

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Smyk, Daniel S., Athanasios Mavropoulos, Giorgina Mieli-Vergani, Diego Vergani, Marco Lenzi, and Dimitrios P. Bogdanos. "The Role of Invariant NKT in Autoimmune Liver Disease: Can Vitamin D Act as an Immunomodulator?" Canadian Journal of Gastroenterology and Hepatology 2018 (June 26, 2018): 1–14. http://dx.doi.org/10.1155/2018/8197937.

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Natural killer T (NKT) cells are a distinct lineage of T cells which express both the T cell receptor (TCR) and natural killer (NK) cell markers. Invariant NKT (iNKT) cells bear an invariant TCR and recognize a small variety of glycolipid antigens presented by CD1d (nonclassical MHC-I). CD1d-restricted iNKT cells are regulators of immune responses and produce cytokines that may be proinflammatory (such as interferon-gamma (IFN-γ)) or anti-inflammatory (such as IL-4). iNKT cells also appear to play a role in B cell regulation and antibody production. Alpha-galactosylceramide (α-GalCer), a deriv

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