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

Item Type:Article
Title:c-Maf controls immune responses by regulating disease-specific gene networks and repressing IL-2 in CD4(+) T cells
Creators Name:Gabryšová, L. and Alvarez-Martinez, M. and Luisier, R. and Cox, L.S. and Sodenkamp, J. and Hosking, C. and Pérez-Mazliah, D. and Whicher, C. and Kannan, Y. and Potempa, K. and Wu, X. and Bhaw, L. and Wende, H. and Sieweke, M.H. and Elgar, G. and Wilson, M. and Briscoe, J. and Metzis, V. and Langhorne, J. and Luscombe, N.M. and O'Garra, A.
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 T(H)1 subset of helper T cells (malaria), T(H)2 cells (allergy) and T(H)17 cells (autoimmunity) in vivo. Although mice with c-Maf deficiency targeted to T cells showed greater pathology in T(H)1 and T(H)2 responses, T(H)17 cell-mediated pathology was reduced in this context, with an accompanying decrease in T(H)17 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 ROR?t (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.
Keywords:CD4-Positive T-Lymphocytes, Gene Regulatory Networks, Interleukin-2, Proto-Oncogene Proteins c-maf, Animals, Mice
Source:Nature Immunology
Publisher:Nature Publishing Group
Page Range:497-507
Date:May 2018
Additional Information:Erratum in: Nat Immunol 20: 374.
Official Publication:https://doi.org/10.1038/s41590-018-0083-5
External Fulltext:View full text on PubMed Central
PubMed:View item in PubMed

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