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

Result code in 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>

Result on the web

<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>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10600 - Biological sciences

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2017

Confidentiality

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

Name of the periodical

Nature

ISSN

0028-0836

e-ISSN

—

Volume of the periodical

546

Issue of the periodical within the volume

7658

Country of publishing house

GB - UNITED KINGDOM

Number of pages

17

Pages from-to

421

UT code for WoS article

000403250900038

EID of the result in the Scopus database

2-s2.0-85020935637