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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F17%3A00100345" target="_blank" >RIV/00216224:14740/17:00100345 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.nature.com/articles/nature22360" target="_blank" >https://www.nature.com/articles/nature22360</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/nature22360" target="_blank" >10.1038/nature22360</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10600 - Biological sciences

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Nature

ISSN

0028-0836

e-ISSN

—

Svazek periodika

546

Číslo periodika v rámci svazku

7658

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

17

Strana od-do

421

Kód UT WoS článku

000403250900038

EID výsledku v databázi Scopus

2-s2.0-85020935637