γδ T lymphocytes, dominant T cell subsets in the intestine, mediate both regulatory and pathogenic roles, yet the mechanisms underlying such opposing effects remain unclear. In this study, we identified a unique γδ T cell subset that coexpresses high levels of gut-homing integrins, CD103 and α4β7. They were exclusively found in the mesenteric lymph node after T cell–mediated colitis induction, and their appearance preceded the inflammation. Adoptive transfer of the CD103+α4β7high subsets enhanced Th1/Th17 T cell generation and accumulation in the intestine, and the disease severity. The level of generation correlated with the disease severity. Moreover, these cells were also found to be elevated in a spontaneous mouse model of ileitis. Based on the procolitogenic function, we referred to this subset as “inflammatory” γδ T cells. Targeting inflammatory γδ T cells may open a novel strategy to treat inflammatory diseases where γδ T cells play a pathogenic role including inflammatory bowel disease.
This work was supported by the Crohn’s Colitis Foundation of America (B.M.) and the National Institutes of Health (Grants DK091222 and DK097948 to T.T.P.).
The online version of this article contains supplemental material.
Abbreviations used in this article:
- inflammatory γδ
- inflammatory bowel disease
- intraepithelial lymphocyte
- lamina propria
- mesenteric lymph node
- peripheral LN
- retinoic acid.
- Received June 17, 2016.
- Accepted November 10, 2016.
- Copyright © 2017 by The American Association of Immunologists, Inc.