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Regulatory T cells suppress CD 4 + T cells through NFAT ‐dependent transcriptional mechanisms
Author(s) -
Shin Daniel S,
Jordan Ayana,
Basu Samik,
Thomas Rajan M,
Bandyopadhyay Sanmay,
Zoeten Edwin F,
Wells Andrew D,
Macian Fernando
Publication year - 2014
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201338233
Subject(s) - nfat , microbiology and biotechnology , t cell , effector , biology , transcription factor , cytokine , il 2 receptor , chemistry , immunology , immune system , gene , biochemistry
Regulatory T cells (Tregs) control autoreactive T cells by inhibiting activation‐induced proliferation and cytokine expression. The molecular mechanisms responsible for the inactivation of effector T cells by Tregs remain yet to be fully characterized. We report that T‐helper cells stimulated in the presence of Tregs quickly activate NFAT 1 and have increased NFAT 1‐dependent expression of the transcription repressor Ikaros. NFAT 1 deficiency or dominant‐negative Ikaros compromises Treg‐mediated inhibition of T‐helper cells in vitro and in vivo . Thus, our results place NFAT ‐dependent mechanisms as general regulators of T‐cell tolerance and show that Treg‐mediated suppression of T‐helper cells results from the activation of NFAT ‐regulated gene expression.