Colitogenic effector T cells: Roles of gut-homing integrin, gut antigen specificity and γδ T cells

Jeong Su Do, Anabelle Visperas, Michael L. Freeman, Yoichiro Iwakura, Mohamed Oukka, Booki Min*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

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 + 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.

Original languageEnglish (US)
Pages (from-to)90-98
Number of pages9
JournalImmunology and Cell Biology
Volume92
Issue number1
DOIs
StatePublished - Jan 2014
Externally publishedYes

Keywords

  • CD4 T cells
  • Colitis
  • Gut antigens
  • IBD
  • α4β7 integrin

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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