Добірка наукової літератури з теми "Innate IELs"

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Статті в журналах з теми "Innate IELs":

1

Qiu, Yuan, Aimin Pu, Hong Zheng, Minqiang Liu, Weigang Chen, Wensheng Wang, Weidong Xiao, and Hua Yang. "TLR2-Dependent Signaling for IL-15 Production Is Essential for the Homeostasis of Intestinal Intraepithelial Lymphocytes." Mediators of Inflammation 2016 (2016): 1–12. http://dx.doi.org/10.1155/2016/4281865.

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TLR2 signaling is related to colitis and involved in regulation of innate immunity in the intestinal tract, but the mechanisms remain unclear. The aim of this study is to investigate how TLR2 affects differentiation of intraepithelial lymphocytes (IELs) and regulates the susceptibility of colitis. IELs were isolated from the small intestine and colon of mice, respectively. The IEL phenotype, activation, and apoptosis were examined using flow cytometry and RT-PCR. IL-15 expression and IEL location were detected through immunohistochemistry. The experimental colitis was induced by administration of dextran sulfate sodium (DSS). We found that the numbers of CD8αα+, CD8αβ+, and TCRγδ+IELs were significantly decreased in TLR2-deficient mice and the residual IELs displayed reduced activation and proliferation and increased apoptosis, accompanied with impaired IL-15 expression by intestinal epithelial cells (IECs). Further study showed that TLR2 signaling maintained the expression of IL-15 in IEC via NF-κB activation. Moreover, TLR2-deficient mice were found to be more susceptible to DSS-induced colitis as shown by the increased severity of colitis. Our results demonstrate that IECs contribute to the maintenance of IELs at least partly via TLR2-dependent IL-15 production, which provides a clue that may link IECs to innate immune protection of the host via IELs.
2

Hummel, Jonas F., Patrice Zeis, Karolina Ebert, Jonas Fixemer, Philip Konrad, Christian Schachtrup, Sebastian J. Arnold, Dominic Grün, and Yakup Tanriver. "Single-cell RNA-sequencing identifies the developmental trajectory of C-Myc-dependent NK1.1− T-bet+ intraepithelial lymphocyte precursors." Mucosal Immunology 13, no. 2 (November 2019): 257–70. http://dx.doi.org/10.1038/s41385-019-0220-y.

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Abstract Natural intraepithelial lymphocytes (IELs) are thymus-derived adaptive immune cells, which are important contributors to intestinal immune homeostasis. Similar to other innate-like T cells, they are induced in the thymus through high-avidity interaction that would otherwise lead to clonal deletion in conventional CD4 and CD8 T cells. By applying single-cell RNA-sequencing (scRNA-seq) on a heterogeneous population of thymic CD4−CD8αβ−TCRαβ+NK1.1− IEL precursors (NK1.1− IELPs), we define a developmental trajectory that can be tracked based on the sequential expression of CD122 and T-bet. Moreover, we identify the Id proteins Id2 and Id3 as a novel regulator of IELP development and show that all NK1.1− IELPs progress through a PD-1 stage that precedes the induction of T-bet. The transition from PD-1 to T-bet is regulated by the transcription factor C-Myc, which has far reaching effects on cell cycle, energy metabolism, and the translational machinery during IELP development. In summary, our results provide a high-resolution molecular framework for thymic IEL development of NK1.1− IELPs and deepen our understanding of this still elusive cell type.
3

Kooy-Winkelaar, Yvonne M. C., Dagmar Bouwer, George M. C. Janssen, Allan Thompson, Martijn H. Brugman, Frederike Schmitz, Arnoud H. de Ru, et al. "CD4 T-cell cytokines synergize to induce proliferation of malignant and nonmalignant innate intraepithelial lymphocytes." Proceedings of the National Academy of Sciences 114, no. 6 (January 2017): E980—E989. http://dx.doi.org/10.1073/pnas.1620036114.

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Refractory celiac disease type II (RCDII) is a severe complication of celiac disease (CD) characterized by the presence of an enlarged clonal population of innate intraepithelial lymphocytes (IELs) lacking classical B-, T-, and natural killer (NK)-cell lineage markers (Lin−IELs) in the duodenum. In ∼50% of patients with RCDII, these Lin−IELs develop into a lymphoma for which no effective treatment is available. Current evidence indicates that the survival and expansion of these malignant Lin−IELs is driven by epithelial cell-derived IL-15. Like CD, RCDII is strongly associated with HLA-DQ2, suggesting the involvement of HLA-DQ2–restricted gluten-specific CD4+ T cells. We now show that gluten-specific CD4+ T cells isolated from CD duodenal biopsy specimens produce cytokines able to trigger proliferation of malignant Lin−IEL lines as powerfully as IL-15. Furthermore, we identify TNF, IL-2, and IL-21 as CD4+ T-cell cytokines that synergistically mediate this effect. Like IL-15, these cytokines were found to increase the phosphorylation of STAT5 and Akt and transcription of antiapoptotic mediator bcl-xL. Several small-molecule inhibitors targeting the JAK/STAT pathway blocked proliferation elicited by IL-2 and IL-15, but only an inhibitor targeting the PI3K/Akt/mTOR pathway blocked proliferation induced by IL-15 as well as the CD4+ T-cell cytokines. Confirming and extending these findings, TNF, IL-2, and IL-21 also synergistically triggered the proliferation of freshly isolated Lin−IELs and CD3−CD56+ IELs (NK-IELs) from RCDII as well as non-RCDII duodenal biopsy specimens. These data provide evidence implicating CD4+ T-cell cytokines in the pathogenesis of RCDII. More broadly, they suggest that adaptive immune responses can contribute to innate IEL activation during mucosal inflammation.
4

Jiang, Wei, Xiaqiong Wang, Benhua Zeng, Lei Liu, Aubry Tardivel, Hong Wei, Jiahuai Han, et al. "Recognition of gut microbiota by NOD2 is essential for the homeostasis of intestinal intraepithelial lymphocytes." Journal of Experimental Medicine 210, no. 11 (September 2013): 2465–76. http://dx.doi.org/10.1084/jem.20122490.

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NOD2 functions as an intracellular sensor for microbial pathogen and plays an important role in epithelial defense. The loss-of-function mutation of NOD2 is strongly associated with human Crohn’s disease (CD). However, the mechanisms of how NOD2 maintains the intestinal homeostasis and regulates the susceptibility of CD are still unclear. Here we found that the numbers of intestinal intraepithelial lymphocytes (IELs) were reduced significantly in Nod2−/− mice and the residual IELs displayed reduced proliferation and increased apoptosis. Further study showed that NOD2 signaling maintained IELs via recognition of gut microbiota and IL-15 production. Notably, recovery of IELs by adoptive transfer could reduce the susceptibility of Nod2−/− mice to the 2,4,6-trinitrobenzene sulfonic acid (TNBS)–induced colitis. Our results demonstrate that recognition of gut microbiota by NOD2 is important to maintain the homeostasis of IELs and provide a clue that may link NOD2 variation to the impaired innate immunity and higher susceptibility in CD.
5

Losurdo, Giuseppe, Domenico Piscitelli, Federica Pezzuto, Francesco Fortarezza, Claudia Covelli, Antonella Marra, Andrea Iannone, et al. "T Helper Lymphocyte and Mast Cell Immunohistochemical Pattern in Nonceliac Gluten Sensitivity." Gastroenterology Research and Practice 2017 (2017): 1–9. http://dx.doi.org/10.1155/2017/5023680.

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Background and Aims. Nonceliac gluten sensitivity (NCGS) is a gluten-related emerging condition. Since few data about NCGS histopathology is available, we assessed the markers of lymphocyte and innate immunity activation. Materials and Methods. We retrieved duodenal biopsy samples of patients with NCGS diagnosis according to the Salerno criteria. We selected specimens of positive (seropositive celiac disease/Marsh 1-2 stage) and negative (normal microscopic picture) controls. Immunohistochemistry for CD3 (intraepithelial lymphocytes-IELs), CD4 (T helper lymphocytes), CD8 (T cytotoxic lymphocytes), and CD1a/CD117 (Langerhans/mast cells) was performed. ANOVA plus Bonferroni’s tests were used for statistical analysis. Results. Twenty NCGS, 16 celiac disease, and 16 negative controls were selected. CD3 in NCGS were higher than negative controls and lower than celiac disease (18.5 ± 6.4, 11.9 ± 2.8, and 40.8 ± 8.1 IELs/100 enterocytes; p<0.001). CD4 were lower in NCGS than controls and celiac disease (31.0 ± 22.1, 72.5 ± 29.5, and 103.7 ± 15.7 cells/mm2; p<0.001). CD8 in NCGS were similar to negative controls, but lower than celiac disease (14.0 ± 7.4 and 34.0 ± 7.1 IELs/100 enterocytes, p<0.001). CD117 were higher in NCGS than celiac disease and negative controls (145.8 ± 49.9, 121.3 ± 13.1, and 113.5 ± 23.4 cells/mm2; p=0.009). Conclusions. The combination of CD4 and CD117, as well as IEL characterization, may be useful to support a clinical diagnosis of NCGS.
6

Kisielow, Jan, Luigi Tortola, Jacqueline Weber, Klaus Karjalainen та Manfred Kopf. "Evidence for the divergence of innate and adaptive T-cell precursors before commitment to the αβ and γδ lineages". Blood 118, № 25 (грудень 2011): 6591–600. http://dx.doi.org/10.1182/blood-2011-05-352732.

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Abstract In addition to adaptive T cells, the thymus supports the development of unconventional T cells such as natural killer T (NKT) and CD8αα intraepithelial lymphocytes (IELs), which have innate functional properties, particular antigenic specificities, and tissue localization. Both conventional and innate T cells are believed to develop from common precursors undergoing instructive, TCR-mediated lineage fate decisions, but innate T cells are proposed to undergo positive instead of negative selection in response to agonistic TCR signals. In the present study, we show that, in contrast to conventional αβT cells, innate αβT cells are not selected against functional TCRγ rearrangements and express TCRγ mRNA. Likewise, in contrast to the majority of γδT cells, thymic innate γδT cells are not efficiently selected against functional TCRβ chains. In precursors of conventional T cells, autonomous TCR signals emanating from the pre-TCR or γδTCR in the absence of ligand mediate selection against the TCR of the opposite isotype and αβ/γδ lineage commitment. Our data suggest that developing innate T cells ignore such signals and rely solely on agonistic TCR interactions. Consistently, most innate T cells reacted strongly against autologous thymocytes. These results suggest that innate and adaptive T-cell lineages do not develop from the same pool of precursors and potentially diverge before αβ/γδ lineage commitment.
7

Billiet, Lore, Glenn Goetgeluk, Sarah Bonte, Stijn De Munter, Laurenz De Cock, Melissa Pille, Joline Ingels, et al. "Human Thymic CD10+ PD-1+ Intraepithelial Lymphocyte Precursors Acquire Interleukin-15 Responsiveness at the CD1a– CD95+ CD28– CCR7– Developmental Stage." International Journal of Molecular Sciences 21, no. 22 (November 2020): 8785. http://dx.doi.org/10.3390/ijms21228785.

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Human thymic CD8αα+ CD10+ PD-1+ αβ T cells selected through early agonist selection have been proposed as the putative thymic precursors of the human CD8αα+ intestinal intraepithelial lymphocytes (IELs). However, the progeny of these thymic precursor cells in human blood or tissues has not yet been characterized. Here, we studied the phenotypical and transcriptional differentiation of the thymic IEL precursor (IELp) lineage upon in vitro exposure to cytokines prominent in the peripheral tissues such as interleukin-15 (IL-15) and the inflammatory cytokines interleukin-12 (IL-12) and interleukin-18 (IL-18). We showed that only the CD1a− fraction of the CD10+ PD-1+ IELp population was able to proliferate with IL-15, suggesting that this subset had acquired functionality. These cells downregulated PD-1 expression and completely lost CD10 expression, whereas other surface markers such as CD95 and CXCR3 remained highly expressed. RNA-seq analysis of the IL-15-cultured cells clearly showed induction of innate-like and effector genes. Induction of the cytotoxic machinery by the CD10+ PD-1+ population was acquired in the presence of IL-15 and was further augmented by inflammatory cytokines. Our data suggest that only the CD1a− CD10+ PD-1+ population exits the thymus and survives in the periphery. Furthermore, PD-1 and CD10 expression is not an intrinsic property of this lineage, but rather characterizes a transient stage in differentiation. CD95 and CXCR3 expression combined with the absence of CD28, CCR7, and CD6 expression might be more powerful markers to define this lineage in the periphery.
8

Clarizio, A. V., H. J. Galipeau, J. Jury, L. Rondeau, J. Godbout, L. Williams, B. Anderson, and E. Verdu. "A19 NOVEL HLA-DQ2 TRANSGENIC MICE DEVELOP GLUTEN-IMMUNOPATHOLOGY FOLLOWING GLUTEN SENSITIZATION." Journal of the Canadian Association of Gastroenterology 3, Supplement_1 (February 2020): 22–23. http://dx.doi.org/10.1093/jcag/gwz047.018.

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Abstract Background Celiac disease (CeD), an autoimmune and chronic inflammatory enteropathy triggered by the ingestion of gluten, is associated with HLA-DQ2 (~90%) and, to a lesser extent, HLA-DQ8. We previously characterized a humanized mouse model of gluten sensitivity that expresses the HLA-DQ8 allele, and that develops mild innate and adaptive immune pathways related to DQ8+ CeD patients. Gluten peptides recognized in the context of DQ2 differ from those bound to DQ8 molecules and homozygous carriage of HLA-DQ2 provides higher risk for CeD development. Thus, characterization of a transgenic HLA-DQ2 model would allow for the investigation of disease pathways that affect the majority of celiac patients. Aims Our aim was to determine gluten-immune responses and small intestinal pathology in C57BL/6 mice humanized with the HLA DR3-DQ2 gene. Methods To break oral tolerance to gluten, DR3-DQ2 mice were orally sensitized with gliadin (5mg/mL) and cholera toxin (CT; 2.5mg/mL) before being challenged with gluten (10mg/mL) for three weeks. Non-sensitized DR3-DQ2 controls mice received CT and a sham challenge. To determine the effects of long-term exposure to gluten, gliadin sensitized DR3-DQ2 mice were placed on a gluten-containing diet for twelve weeks. Controls were given CT and remained on a gluten-free diet. Pathology was evaluated by CD3+ intraepithelial lymphocytes (IELs) counts; villus-crypt (V/C) ratios. Gluten-induced immune responses were evaluated by anti-tissue transglutaminase-2 (tTG) and anti-gliadin antibodies, inflammatory gene expression by Nanostring Technology, and CD4+ T cell proliferation using flow cytometry. Intestinal permeability was measured in vitro by Ussing Chamber. Results DR3-DQ2 mice that were sensitized and challenged with gluten for three weeks had higher IEL counts, lower V/C ratios, higher anti-gliadin and tTG antibodies, which are used in the serological diagnosis of the disease. Gluten sensitized mice also has higher expression of pro-inflammatory genes, and an induction of gluten specific T cells, but no changes in permeability compared to control mice. DR3-DQ2 mice given a gluten-containing diet for 12 weeks also had higher IEL counts, lower V/C ratios, and higher anti-gliadin and tTG antibodies, but had no changes in permeability compared to controls. Conclusions These results indicate that mice humanized with the HLA DR3-DQ2 gene show innate and gluten-specific immune responses following sensitization. Thus, mice expressing HLA-DQ2 represents a novel model of gluten sensitivity that can be used to investigate celiac disease pathways related to gluten peptide repertoire that binds to DQ2 MHC class II, encoded by the HLA gene expressed by the majority of celiac patients. Supported by CIHR to EFV and OGS to AVC Funding Agencies CIHROGS
9

Bhinder, Ganive, Martin Stahl, Ho Pan Sham, Shauna M. Crowley, Vijay Morampudi, Udit Dalwadi, Caixia Ma, Kevan Jacobson, and Bruce A. Vallance. "Intestinal Epithelium-Specific MyD88 Signaling Impacts Host Susceptibility to Infectious Colitis by Promoting Protective Goblet Cell and Antimicrobial Responses." Infection and Immunity 82, no. 9 (June 2014): 3753–63. http://dx.doi.org/10.1128/iai.02045-14.

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ABSTRACTIntestinal epithelial cells (IECs), including secretory goblet cells, form essential physiochemical barriers that separate luminal bacteria from underlying immune cells in the intestinal mucosa. IECs are common targets for enteric bacterial pathogens, with hosts responding to these microbes through innate toll-like receptors that predominantly signal through the MyD88 adaptor protein. In fact, MyD88 signaling confers protection against several enteric bacterial pathogens, includingSalmonella entericaserovar Typhimurium andCitrobacter rodentium. Since IECs are considered innately hyporesponsive, it is unclear whether MyD88 signaling within IECs contributes to this protection. We infected mice lacking MyD88 solely in their IECs (IEC-Myd88−/−) withS.Typhimurium. Compared to wild-type (WT) mice, infectedIEC-Myd88−/−mice suffered accelerated tissue damage, exaggerated barrier disruption, and impaired goblet cell responses (Muc2 and RELMβ). Immunostaining revealedS.Typhimurium penetrated the IECs ofIEC-Myd88−/−mice, unlike in WT mice, where they were sequestered to the lumen. When isolated crypts were assayed for their antimicrobial actions, crypts fromIEC-Myd88−/−mice were severely impaired in their antimicrobial activity againstS.Typhimurium. We also examined whether MyD88 signaling in IECs impacted host defense againstC. rodentium, withIEC-Myd88−/−mice again suffering exaggerated tissue damage, impaired goblet cell responses, and reduced antimicrobial activity againstC. rodentium. These results demonstrate that MyD88 signaling within IECs plays an important protective role at early stages of infection, influencing host susceptibility to infection by controlling the ability of the pathogen to reach and survive at the intestinal mucosal surface.
10

Hosomi, Shuhei, Joep Grootjans, Markus Tschurtschenthaler, Niklas Krupka, Juan D. Matute, Magdalena B. Flak, Eduardo Martinez-Naves, et al. "Intestinal epithelial cell endoplasmic reticulum stress promotes MULT1 up-regulation and NKG2D-mediated inflammation." Journal of Experimental Medicine 214, no. 10 (July 2017): 2985–97. http://dx.doi.org/10.1084/jem.20162041.

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Endoplasmic reticulum (ER) stress is commonly observed in intestinal epithelial cells (IECs) and can, if excessive, cause spontaneous intestinal inflammation as shown by mice with IEC-specific deletion of X-box–binding protein 1 (Xbp1), an unfolded protein response–related transcription factor. In this study, Xbp1 deletion in the epithelium (Xbp1ΔIEC) is shown to cause increased expression of natural killer group 2 member D (NKG2D) ligand (NKG2DL) mouse UL16-binding protein (ULBP)–like transcript 1 and its human orthologue cytomegalovirus ULBP via ER stress–related transcription factor C/EBP homology protein. Increased NKG2DL expression on mouse IECs is associated with increased numbers of intraepithelial NKG2D-expressing group 1 innate lymphoid cells (ILCs; NK cells or ILC1). Blockade of NKG2D suppresses cytolysis against ER-stressed epithelial cells in vitro and spontaneous enteritis in vivo. Pharmacological depletion of NK1.1+ cells also significantly improved enteritis, whereas enteritis was not ameliorated in Recombinase activating gene 1−/−;Xbp1ΔIEC mice. These experiments reveal innate immune sensing of ER stress in IECs as an important mechanism of intestinal inflammation.

Дисертації з теми "Innate IELs":

1

Hariss, Fatima. "Etude du rôle des Lymphocytes Intraépithéliaux innés dans la réponse immune protectrice contre Cryptosporidium parvum." Electronic Thesis or Diss., Université de Lille (2018-2021), 2021. http://www.theses.fr/2021LILUS047.

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Les lymphocytes intraépithéliaux (LIE) résident entre les cellules épithéliales (CE) intestinales et sont donc les premières cellules immunitaires à entrer en contact avec les agents pathogènes. En plus de répondre rapidement à l'infection, ils régulent l'homéostasie intestinale et maintiennent la barrière épithéliale. Ces fonctions sont assurées par différentes sous-populations de lymphocytes T et innés. Les LIE innés ont été identifiés récemment. Ils sont majoritaires dans l'épithélium intestinal à la naissance et lorsque l'immunité adaptative est compromise. Leur rôle dans la réponse immunitaire contre les pathogènes intestinaux reste cependant peu étudié.Au cours de ma thèse, j'ai étudié le rôle des LIE innés dans l'infection à Cryptosporidium, un parasite opportuniste qui infecte l'épithélium intestinal. L'infection est bénigne chez les individus immunocompétents, mais peut être sévère chez les individus immunodéprimés et les enfants.Pour étudier le rôle spécifique des LIE innés, nous avons développé un modèle in vitro qui consiste à co-cultiver des organoïdes intestinaux murins infectés par C parvum avec des LIE innés de souris RAG2-/-. Grâce à ce modèle original, nous avons démontré que les LIE innés contrôlent la prolifération du parasite et bien qu’ils sécrètent l'IFN-ƴ en réponse à C parvum, cette sécrétion n’est pas suffisante pour inhiber la prolifération du parasite. L'effet protecteur des LIE innés est en fait médié par un mécanisme cytotoxique dépendant des granzymes. L’analyse du transcriptome a révélé que les CE infectées régulent négativement la serpinb9b, un inhibiteur de granzyme, et pourraient ainsi être plus sensibles aux attaques cytotoxiques
Intraepithelial lymphocytes (IEL) reside between intestinal epithelial cells and thus are the first immune cells to contact intestinal pathogens. In addition to respond rapidly to infection, they regulate intestinal homeostasis and maintain the epithelial barrier. This wide range of functions is achieved by distinct subsets of T and innate lymphocytes. Innate IEL which share many features with NK/ILC1 cells have been identified recently. These cells dominate the gut epithelium at birth and when the adaptive immunity is compromised. Their role in the immune response against intestinal pathogens remains however poorly studied.During my PhD thesis, I have investigated the role of innate IEL subsets in Crysptosporidium infection. Crysptosporidium is a common parasite that infects the gut epithelium. The infection is self-limiting in immunocompetent individuals, but it can be severe in immunocompromised individuals and children in whom innate IEL dominate.To study the specific role of innate IEL, we have developed an in vitro model that consist to co-culture mice 3D intestinal organoids infected with C parvum with innate IELs from RAG2-/- mice. Thanks to this original model, we demonstrated that innate IELs control parasite proliferation. We further showed that although innate IEL secrete IFN-ƴ in response to C parvum infection, the IFN-ƴ secretion was not sufficient to inhibit parasite proliferation. The protective effect of innate IELs was in fact mediated by a cytotoxic, granzyme-dependent mechanism. Moreover, transcriptomic analysis revealed that infected epithelial cells down regulated serpinb9b, a granzyme inhibitor, and thus may be more sensitive to cytotoxic attack
2

Pietz, Grzegorz. "Innate immunity of human intestinal epithelium in childhood celiac disease : influences from celiac disease associated bacteria and dietary oats." Doctoral thesis, comprehensive summary, Umeå universitet, Institutionen för molekylärbiologi (Medicinska fakulteten), 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-140691.

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Background & Aims: Celiac disease (CD) is a chronic inflammatory small-bowel enteropathy caused by permanent intolerance to gliadin in wheat gluten, and related proteins in ray and barley. It is disputed whether CD patients tolerate oats. The only treatment of CD is lifelong gluten-free diet (GFD). Only individuals that carry the HLA-DQ2 and/or DQ8 alleles, and eat gluten can develop CD. Dysbiosis in the gut microbiota is a suggested risk factor for CD. T cells in small intestinal mucosa, including intraepithelial lymphocytes (IELs), are known to be important in the pathogenesis of CD. In contrast, the role of intestinal epithelial cells (IECs) is poorly understood. In this thesis we investigated the role of IECs in the immune pathology of CD from duodenal mucosa of children with CD, clinical controls and treated CD. We also investigated the role of CD associated bacteria and oats supplemented GFD on the mucosal immune system. Results: A new CD-associated bacterium, Prevotella jejuni, was isolated and characterized. It is a saccharolytic and proteolytic anaerobe. More than 25 defense-related genes, including IRF1, SPINK4, ITLN1, OAS2, CIITA, HLA-DMB, HLA-DOB, PSMB9, TAP1, BTN3A1, and CX3CL1, were upregulated in IECs in active CD. In two in vitro models for intestinal epithelium, small intestine enteroids and T84 polarized tight monolayers, we showed that 70% of these genes were upregulated by interferon (IFN)-γ via the IRF1 pathway. IRF1 was also upregulated by the CD-associated bacteria P. jejuni and Actinomyces gravenitzii. IECs expressed the NLRP6/8 inflammasome yielding CASP1 and biologically active interleukin (IL)-18, which induces IFN-γ in IELs. P. jejuni bound the intestinal epithelial cell lines T84, Caco2, HT29, and INT407, while Lachnoanaerobaculum umeaense preferentially bound Caco2. P. jejuni caused decreased transepithelial resistance over tight monolayers, while L. umeaense caused an increase. P. jejuni upregulated mRNAs for the detoxification molecules CYP1A1, CYP1A2, CYP1B1, and TIPARP, the chemokines CX3CL1, CXCL1, and CXCL10, the sialyltranserase ST3GAL4, and the inflammation promoting protein S100A3 in tight monolayers. L. umeaense upregulated the chemokines CCL20 and CXCL10, and down-regulated TLR2. In a randomized, double-blinded intervention trial comparing two study-groups, standard GFD and oat-containing GFD, we found that mRNAs for several immune effector molecules and tight junction proteins were only reduced in patients receiving GFD, but not in a substantial fraction of patients on GFD with oats. The down-regulatory cytokines IL-10 and TGF-β1, the cytotoxicity-activating NK-receptors NKG2C and NKG2E, and the tight junction protein claudin-4 remained elevated in the study group on GFD with oats. Conclusions: IECs are far from inactive in CD. A key factor in the epithelial reaction in CD appears to be over-expression of IRF1 in IECs. Dual activation of IRF1 and IRF1-regulated genes, both directly by P. jejuni and indirectly by IFN-γ via the IL-18-inflammasome, would drastically enhance the inflammatory response and lead to the pathological situation seen in active CD. P. jejuni harms the intestinal epithelium, i.e., it is a likely risk factor for CD, while L. umeaense strengthen barrier function and local immunity, possibly acting as a protective. A fraction of CD patients should avoid oats in the diet.
Doctoral thesis

Книги з теми "Innate IELs":

1

Linden, Mary Anne, and Barbara D. Bateman. Better IEPs: How to Develop Legally Correct and Educationally Useful Programs. 3rd ed. Longmont, CO, USA: Sopris West, 1998.

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