{gamma}{delta} T Cells Coexpressing Gut Homing {alpha}4{beta}7 and {alpha}E Integrins Define a Novel Subset Promoting Intestinal Inflammation [MUCOSAL IMMUNOLOGY]

Abstract

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.

Footnotes

  • 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:

    iγδ
    inflammatory γδ
    IBD
    inflammatory bowel disease
    IEL
    intraepithelial lymphocyte
    LP
    lamina propria
    mLN
    mesenteric lymph node
    pLN
    peripheral LN
    RA
    retinoic acid.
  • Received June 17, 2016.
  • Accepted November 10, 2016.

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