title: The inhibitory receptor BTLA controls γδ T cell homeostasis and inflammatory responses.
abstract: γδ 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 (RORγt) and interleukin-7 (IL-7) influence γδ T cell homeostasis and function by regulating expression of the inhibitory receptor, B and T lymphocyte attenuator (BTLA). The transcription factor RORγt, via its activating function-2 domain, repressed Btla transcription, whereas IL-7 increased BTLA levels on the cell surface. BTLA expression limited γδ T cell numbers and sustained normal γδ T cell subset frequencies by restricting IL-7 responsiveness and expansion of the CD27(-)RORγt(+) population. BTLA also negatively regulated IL-17 and TNF production in CD27(-) γδ T cells. Consequently, BTLA-deficient mice exhibit enhanced disease in a γδ T cell-dependent model of dermatitis, whereas BTLA agonism reduced inflammation. Therefore, by coordinating expression of BTLA, RORγt and IL-7 balance suppressive and activation stimuli to regulate γδ T cell homeostasis and inflammatory responses.
authors: Infectious and Inflammatory Diseases Center, Sanford|Burnham Medical Research Institute, 10901 N. Torrey Pines Road, La Jolla, CA 92037, USA.
authors: Vasileios
authors: V
authors: Bekiaris
authors: Infectious and Inflammatory Diseases Center, Sanford|Burnham Medical Research Institute, 10901 N. Torrey Pines Road, La Jolla, CA 92037, USA.
authors: John R
authors: JR
authors: Šedý
authors: Infectious and Inflammatory Diseases Center, Sanford|Burnham Medical Research Institute, 10901 N. Torrey Pines Road, La Jolla, CA 92037, USA.
authors: Matthew G
authors: MG
authors: Macauley
authors: Infectious and Inflammatory Diseases Center, Sanford|Burnham Medical Research Institute, 10901 N. Torrey Pines Road, La Jolla, CA 92037, USA.
authors: Antje
authors: A
authors: Rhode-Kurnow
authors: Infectious and Inflammatory Diseases Center, Sanford|Burnham Medical Research Institute, 10901 N. Torrey Pines Road, La Jolla, CA 92037, USA.
authors: Carl F
authors: CF
authors: Ware
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005434:Flow Cytometry; D017353:Gene Deletion; D006706:Homeostasis; D006801:Humans; D007249:Inflammation; D051379:Mice; D008810:Mice, Inbred C57BL; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
chemical_list: C488868:BTLA protein, mouse; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011971:Receptors, Immunologic