Informace o publikaci

Stability and function of regulatory T cells expressing the transcription factor T-bet

Autoři	LEVINE A.G. MEDOZA A. HEMMERS S. MOLTEDO B. NIEC R.E. SCHIZAS M. HOYOS B.E. PUTINTSEVA E.V. CHAUDHRY A. DIKIY S. FUJISAWA S. CHUDAKOV Dmitriy TREUTING P.M. RUDENSKY A.Y.
Rok publikování	2017
Druh	Článek v odborném periodiku
Časopis / Zdroj	Nature
Fakulta / Pracoviště MU	Středoevropský technologický institut
Citace
www	https://www.nature.com/articles/nature22360
Doi	http://dx.doi.org/10.1038/nature22360
Klíčová slova	ROR-GAMMA-T; DIFFERENTIATION; FOXP3; INFECTION; EFFECTOR; IMMUNITY; HOMEOSTASIS; GENERATION; GATA-3
Popis	Adaptive immune responses are tailored to different types of pathogens through differentiation of naive CD4 T cells into functionally distinct subsets of effector T cells (T helper 1 (T(H)1), T(H)2, and T(H)17) defined by expression of the key transcription factors T-bet, GATA3, and ROR gamma t, respectively(1). Regulatory T (T-reg) cells comprise a distinct anti-inflammatory lineage specified by the X-linked transcription factor Foxp3 (refs 2, 3). Paradoxically, some activated T-reg cells express the aforementioned effector CD4 T cell transcription factors, which have been suggested to provide T-reg cells with enhanced suppressive capacity(4-6). Whether expression of these factors in T-reg cells-as in effector T cells-is indicative of heterogeneity of functionally discrete and stable differentiation states, or conversely may be readily reversible, is unknown. Here we demonstrate that expression of the T(H)1-associated transcription factor T-bet in mouse T-reg cells, induced at steady state and following infection, gradually becomes highly stable even under non-permissive conditions. Loss of function or elimination of T-bet-expressing T-reg cells-but not of T-bet expression in T-reg cells-resulted in severe T(H)1 autoimmunity. Conversely, following depletion of T-bet-T-reg cells, the remaining T-bet(+) cells specifically inhibited T(H)1 and CD8 T cell activation consistent with their co-localization with T-bet(+) effector T cells. These results suggest that T-bet(+) T-reg cells have an essential immunosuppressive function and indicate that T-reg cell functional heterogeneity is a critical feature of immunological tolerance.