The role of IL-17-producing Foxp3+ CD4+ T cells in inflammatory bowel disease and colon cancer

AbstractTumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces cell apoptosis by transducing apoptosis signals. Recently, accumulating evidence demonstrated that TRAIL regulates autoimmune inflammation and immune cell homeostasis in several autoimmune animal models, suggesting a novel immunoregulatory role of TRAIL in autoimmune diseases. However, the impact of TRAIL in inflammatory bowel disease is yet undefined. This study is to address the therapeutic effects and immunoregulatory role of TRAIL in autoimmune gut inflammation. We demonstrated herein that TRAIL significantly suppressed gut inflammation and reduced the severity of colitis in a dextran sodium sulfate (DSS)-induced colitis model. Suppression of gut inflammation was not due to induction of apoptosis in colonic T cells, dendritic cells, or epithelium cells by TRAIL. In contrast, TRAIL directly inhibited activation of colitogenic T cells and development of gut inflammation in an adoptive transfer-induced colitis model. The anti-inflammatory effects of TRAIL on colitis were abolished when T cells from TRAIL receptor (TRAIL-R) knockout mice were adoptively transferred, suggesting that TRAIL regulates autoreactive colitogenic T-cell activation in the development of gut inflammation. Our results demonstrate that TRAIL effectively inhibited colonic T-cell activation and suppressed autoimmune colitis, suggesting a potential therapeutic application of TRAIL in human inflammatory bowel disease.

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Exclusive increase of CX3CR1+CD28−CD4+ T cells in inflammatory bowel disease and their recruitment as intraepithelial lymphocytes

Inflammatory Bowel Diseases ◽

10.1002/ibd.20113 ◽

2007 ◽

Vol 13 (7) ◽

pp. 837-846 ◽

Cited By ~ 54

Author(s):

Taku Kobayashi ◽

Susumu Okamoto ◽

Yuko Iwakami ◽

Atsushi Nakazawa ◽

Tadakazu Hisamatsu ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

T Cells ◽

Bowel Disease ◽

Cd4 T Cells ◽

Intraepithelial Lymphocytes ◽

Inflammatory Bowel

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IL-10 signaling in dendritic cells controls IL-1β-mediated IFNγ secretion by human CD4+ T cells: relevance to inflammatory bowel disease

Mucosal Immunology ◽

10.1038/s41385-019-0194-9 ◽

2019 ◽

Vol 12 (5) ◽

pp. 1201-1211 ◽

Cited By ~ 10

Author(s):

S. Veenbergen ◽

P. Li ◽

H. C. Raatgeep ◽

D. J. Lindenbergh-Kortleve ◽

Y. Simons-Oosterhuis ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

T Cells ◽

Dendritic Cells ◽

Bowel Disease ◽

Cd4 T Cells ◽

Inflammatory Bowel

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Peripheral and Intestinal CD4+ T Cells With a Regulatory Phenotype in Pediatric Patients With Inflammatory Bowel Disease

Journal of Pediatric Gastroenterology and Nutrition ◽

10.1097/mpg.0b013e3181e4d323 ◽

2010 ◽

Vol 51 (5) ◽

pp. 563-572 ◽

Cited By ~ 11

Author(s):

Raffaella La Scaleia ◽

Stefania Morrone ◽

Antonella Stoppacciaro ◽

Stefania Scarpino ◽

Manila Antonelli ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

T Cells ◽

Bowel Disease ◽

Cd4 T Cells ◽

Pediatric Patients ◽

Inflammatory Bowel ◽

Regulatory Phenotype

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New Insights on CD8+ T Cells in Inflammatory Bowel Disease and Therapeutic Approaches

Frontiers in Immunology ◽

10.3389/fimmu.2021.738762 ◽

2021 ◽

Vol 12 ◽

Author(s):

Rosaely Casalegno Garduño ◽

Jan Däbritz

Keyword(s):

Inflammatory Bowel Disease ◽

T Cells ◽

Cd8 T Cells ◽

Bowel Disease ◽

Positive Outcome ◽

T Cell Subsets ◽

Therapeutic Approaches ◽

Therapeutic Value ◽

Inflammatory Bowel

CD8+ T cells are involved in the pathogenesis of inflammatory bowel disease (IBD), a complex multifactorial chronic disease. Here, we present an overview of the current research with the controversial findings of CD8+ T cell subsets and discuss some possible perspectives on their therapeutic value in IBD. Studies on the role of CD8+ T cells in IBD have contradictory outcomes, which might be related to the heterogeneity of the cells. Recent data suggest that cytotoxic CD8+ T cells (Tc1) and interleukin (IL) 17-producing CD8+ (Tc17) cells contribute to the pathogenesis of IBD. Moreover, subsets of regulatory CD8+ T cells are abundant at sites of inflammation and can exhibit pro-inflammatory features. Some subsets of tissue resident memory CD8+ T cells (Trm) might be immunosuppressant, whereas others might be pro-inflammatory. Lastly, exhausted T cells might indicate a positive outcome for patients. The function and plasticity of different subsets of CD8+ T cells in health and IBD remain to be further investigated in a challenging field due to the limited availability of mucosal samples and adequate controls.

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The Mechanisms of Up-Regulation of K+ Channels in CD4+ T Cells of Inflammatory Bowel Disease

Biophysical Journal ◽

10.1016/j.bpj.2019.11.2369 ◽

2020 ◽

Vol 118 (3) ◽

pp. 420a

Author(s):

Susumu Ohya ◽

Kyoko Endo ◽

Hiroaki Kito ◽

Junko Kajikuri ◽

Takayoshi Suzuki

Keyword(s):

Inflammatory Bowel Disease ◽

T Cells ◽

Bowel Disease ◽

Cd4 T Cells ◽

K Channels ◽

Inflammatory Bowel

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Ontogeny, function, and peripheral homeostasis of regulatory T cells in the absence of interleukin-7

Blood ◽

10.1182/blood-2006-04-017947 ◽

2006 ◽

Vol 108 (7) ◽

pp. 2300-2306 ◽

Cited By ~ 33

Author(s):

Régis Peffault de Latour ◽

Hélène C. Dujardin ◽

Florence Mishellany ◽

Odile Burlen-Defranoux ◽

Julien Zuber ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

T Cells ◽

T Cell ◽

Bowel Disease ◽

Cd4 T Cells ◽

Cell Subset ◽

Thymic Involution ◽

Cell Compartment ◽

Interleukin 7 ◽

Inflammatory Bowel

Abstract Mice lacking interleukin-7 (IL-7–/– mice) have no signs of autoimmune disease, contrary to other models of lymphopenia. We investigated whether the absence of disease was due to the fact that IL-7 is dispensable for the ontogeny, function, and homeostasis of regulatory CD4+ T cells. We show here that the establishment of the peripheral pool of Foxp3-expressing regulatory cells is IL-7 independent, and the premature involution of the thymus in IL-7–/– mice does not change the representation of the CD4+CD25+ T-cell compartment. In addition, CD4+CD25+ T cells expand in the absence of IL-7, without losing Foxp3 expression. The frequency of activated peripheral CD4+ T cells increases with age in both the CD25– and CD25+ compartments, with the CD4+CD25+ T cells displaying signs of constant activation. IL-7–/– CD4+CD25+ T cells control inflammatory bowel disease induced by IL-7–/– T cells even in hosts lacking IL-7. Depletion of the CD25+ T-cell subset after thymic involution results in a mild form of inflammatory bowel disease (IBD), which resolves concomitantly with the regeneration of this subset. This study shows for the first time that IL-7–/– mice have a robust regulatory Foxp3-expressing CD4+ T-cell compartment that controls T-cell–mediated disease. It also highlights the potential of the regulatory Foxp3-expressing CD4+CD25– T-cell population to restore a functional CD4+CD25+ T-cell compartment through an IL-7–independent pathway.

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