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Elvira Kurmaeva, Moheb Boktor, Songling Zhang, Richard Bao, Seth Berney, Dmitry V. Ostanin, Roles of T cell–Associated L-selectin and β7 Integrins During Induction and Regulation of Chronic Colitis, Inflammatory Bowel Diseases, Volume 19, Issue 12, 1 November 2013, Pages 2547–2559, https://doi.org/10.1097/MIB.0b013e3182a8df0a
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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.
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.
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 wild-type T cells.
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.
