The inhibitory receptor BTLA controls ?? T cell homeostasis and inflammatory responses.

ABSTRACT: ?? T cells rapidly secrete inflammatory cytokines at barrier sites that aid in protection from pathogens, but mechanisms limiting inflammatory damage remain unclear. We found that retinoid-related orphan receptor gamma-t (ROR?t) and interleukin-7 (IL-7) influence ?? T cell homeostasis and function by regulating expression of the inhibitory receptor, B and T lymphocyte attenuator (BTLA). The transcription factor ROR?t, via its activating function-2 domain, repressed Btla transcription, whereas IL-7 increased BTLA levels on the cell surface. BTLA expression limited ?? T cell numbers and sustained normal ?? T cell subset frequencies by restricting IL-7 responsiveness and expansion of the CD27(-)ROR?t(+) population. BTLA also negatively regulated IL-17 and TNF production in CD27(-) ?? T cells. Consequently, BTLA-deficient mice exhibit enhanced disease in a ?? T cell-dependent model of dermatitis, whereas BTLA agonism reduced inflammation. Therefore, by coordinating expression of BTLA, ROR?t and IL-7 balance suppressive and activation stimuli to regulate ?? T cell homeostasis and inflammatory responses.

SUBMITTER: Bekiaris V 

PROVIDER: S-EPMC3909738 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature