| First Author | Bekiaris V | Year | 2013 |
| Journal | Immunity | Volume | 39 |
| Issue | 6 | Pages | 1082-1094 |
| PubMed ID | 24315996 | Mgi Jnum | J:209301 |
| Mgi Id | MGI:5566939 | Doi | 10.1016/j.immuni.2013.10.017 |
| Citation | Bekiaris V, et al. (2013) The inhibitory receptor BTLA controls gammadelta T cell homeostasis and inflammatory responses. Immunity 39(6):1082-94 |
| abstractText | gammadelta 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 (RORgammat) and interleukin-7 (IL-7) influence gammadelta T cell homeostasis and function by regulating expression of the inhibitory receptor, B and T lymphocyte attenuator (BTLA). The transcription factor RORgammat, via its activating function-2 domain, repressed Btla transcription, whereas IL-7 increased BTLA levels on the cell surface. BTLA expression limited gammadelta T cell numbers and sustained normal gammadelta T cell subset frequencies by restricting IL-7 responsiveness and expansion of the CD27(-)RORgammat(+) population. BTLA also negatively regulated IL-17 and TNF production in CD27(-) gammadelta T cells. Consequently, BTLA-deficient mice exhibit enhanced disease in a gammadelta T cell-dependent model of dermatitis, whereas BTLA agonism reduced inflammation. Therefore, by coordinating expression of BTLA, RORgammat and IL-7 balance suppressive and activation stimuli to regulate gammadelta T cell homeostasis and inflammatory responses. |
