Roles of T cell-associated L-selectin and β7 integrins during induction and regulation of chronic colitis

Elvira Kurmaeva, Moheb Boktor, Songling Zhang, Richard Bao, Seth Berney, Dmitry V. Ostanin

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Background: L-selectin (CD62L) and β7 integrins are important for trafficking of naive T cells under steady-state conditions. The objectives of this study were to dissect the requirements for T cell-associated CD62L and β7 integrins during initiation, progression, and regulation of chronic colitis. Methods: Using the T-cell transfer model, we compared colitogenic potential between T cells lacking one or both of these molecules with wild-type T cells. To assess trafficking of cells to the secondary lymphoid tissue and the gut, we performed co-homing experiments. Results: Adoptive transfer of wild-type, CD62L-/- or β7-/- single-deficient T cells induced moderate to severe disease with slightly different kinetics. However, transfer of CD62L -/- β7-/- double-deficient (DKO) T cells produced significantly attenuated gut inflammation, which correlated with fewer T cells and reduced levels of proinflammatory cytokines in the colon lamina propria. Our subsequent experiments established that lack of colitogenic potential of these cells was due to inability of DKO T cells to home to the secondary lymphoid tissue. Furthermore, homing of in vitro-generated effector DKO T cells to the inflamed intestine was significantly impaired. Lastly, DKO regulatory T cells were ineffective at suppressing colitis induced by wildtype T cells. Conclusions: We established that T cells can use either CD62L or β7 integrins to induce chronic colitis, but lack of both abrogates their colitogenic potential. Effector T cells critically rely on β7 integrin during their recruitment to the inflamed intestinal mucosa. Finally, regulation of intestinal inflammation by regulatory T cells requires one or both of these adhesion molecules.

Original languageEnglish (US)
Pages (from-to)2547-2559
Number of pages13
JournalInflammatory bowel diseases
Volume19
Issue number12
DOIs
StatePublished - Nov 1 2013
Externally publishedYes

Keywords

  • Adhesion molecules
  • Effector T cell
  • Inflammation
  • Inflammatory bowel disease
  • Leukocyte trafficking

ASJC Scopus subject areas

  • Immunology and Allergy
  • Gastroenterology

Fingerprint Dive into the research topics of 'Roles of T cell-associated L-selectin and β<sub>7</sub> integrins during induction and regulation of chronic colitis'. Together they form a unique fingerprint.

  • Cite this