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Colitogenic effector T cells: roles of gut-homing integrin, gut antigen specificity and γδ T cells.
- Source :
- Immunology & Cell Biology; Jan2014, Vol. 92 Issue 1, p90-98, 9p
- Publication Year :
- 2014
-
Abstract
- Disturbance of T-cell homeostasis could lead to intestinal inflammation. Naive CD4 T cells undergoing spontaneous proliferation, a robust proliferative response that occurs under severe lymphopenic conditions, differentiate into effector cells producing Th1- and/or Th17-type cytokines and induce a chronic inflammation in the intestine that resembles human inflammatory bowel disease. In this study, we investigated the key properties of CD4 T cells necessary to induce experimental colitis. α4β7 upregulation was primarily induced by mesenteric lymph node (mLN) resident CD11b<superscript>+</superscript> dendritic cell subsets via transforming growth factor beta (TGFβ)/retinoic acid-dependent mechanism. Interestingly, α4β7 expression was essential but not sufficient to induce inflammation. In addition to gut-homing specificity, expression of gut Ag specificity was also crucial. T-cell acquisition of the specificity was dramatically enhanced by the presence of γδ T cells, a population previously shown to exacerbate T-cell-mediated colitis. Importantly, interleukin (IL)-23-mediated γδ T cell stimulation was necessary to enhance colitogenicity but not gut antigen reactivity of proliferating CD4 T cells. These findings demonstrate that T-cell colitogenicity is achieved through multiple processes, offering a therapeutic rationale by intervening these pathways. [ABSTRACT FROM AUTHOR]
- Subjects :
- T cells
INTEGRINS
HOMEOSTASIS
CYTOKINES
COLITIS
INFLAMMATORY bowel diseases
Subjects
Details
- Language :
- English
- ISSN :
- 08189641
- Volume :
- 92
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Immunology & Cell Biology
- Publication Type :
- Academic Journal
- Accession number :
- 93504503
- Full Text :
- https://doi.org/10.1038/icb.2013.70