期刊
IMMUNITY
卷 45, 期 4, 页码 831-846出版社
CELL PRESS
DOI: 10.1016/j.immuni.2016.09.018
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类别
资金
- Canadian Institute of Health Research (CIHR) [MOP-130579]
- McGill University Faculty of Medicine
- Fonds de recherche du Quebec-Sante
- Fonds de recherche du Quebec - Nature et Technologies
- Canada Research Chair in Humoral Immunity
T follicular helper (Tfh) cells are a CD4(+) T cell subset critical for long-lived humoral immunity. We hypothesized that integrins play a decisive role in Tfh cell biology. Here we show that Tfh cells expressed a highly active form of leukocyte function-associated antigen-1 (LFA-1) that was required for their survival within the germinal center niche. In addition, LFA-1 promoted expression of Bcl-6, a transcriptional repressor critical for Tfh cell differentiation, and inhibition of LFA-1 abolished Tfh cell generation and prevented protective humoral immunity to intestinal helminth infection. Furthermore, we demonstrated that expression of Talin-1, an adaptor protein that regulates LFA-1 affinity, dictated Tfh versus Th2 effector cell differentiation. Collectively, our results define unique functions for LFA-1 in the Tfh cell effector program and suggest that integrin activity is important in lineage decision-making events in the adaptive immune system.
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