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c-Maf controls immune responses by regulating disease-specific gene networks and repressing IL-2 in CD4+ T cells.

Abstract：

:The transcription factor c-Maf induces the anti-inflammatory cytokine IL-10 in CD4+ T cells in vitro. However, the global effects of c-Maf on diverse immune responses in vivo are unknown. Here we found that c-Maf regulated IL-10 production in CD4+ T cells in disease models involving the TH1 subset of helper T cells (malaria), TH2 cells (allergy) and TH17 cells (autoimmunity) in vivo. Although mice with c-Maf deficiency targeted to T cells showed greater pathology in TH1 and TH2 responses, TH17 cell-mediated pathology was reduced in this context, with an accompanying decrease in TH17 cells and increase in Foxp3+ regulatory T cells. Bivariate genomic footprinting elucidated the c-Maf transcription-factor network, including enhanced activity of NFAT; this led to the identification and validation of c-Maf as a negative regulator of IL-2. The decreased expression of the gene encoding the transcription factor RORγt (Rorc) that resulted from c-Maf deficiency was dependent on IL-2, which explained the in vivo observations. Thus, c-Maf is a positive and negative regulator of the expression of cytokine-encoding genes, with context-specific effects that allow each immune response to occur in a controlled yet effective manner.

journal_name

Nat Immunol

journal_title

Nature immunology

authors

Gabryšová L,Alvarez-Martinez M,Luisier R,Cox LS,Sodenkamp J,Hosking C,Pérez-Mazliah D,Whicher C,Kannan Y,Potempa K,Wu X,Bhaw L,Wende H,Sieweke MH,Elgar G,Wilson M,Briscoe J,Metzis V,Langhorne J,Luscombe NM,O'Garra

doi

10.1038/s41590-018-0083-5

subject

Has Abstract

pub_date

2018-05-01 00:00:00

pages

497-507

issue

5

eissn

1529-2908

issn

1529-2916

pii

10.1038/s41590-018-0083-5

journal_volume

19

pub_type

杂志文章

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