Details

Autor(en) / Beteiligte

• Gabryšová, Leona
• Alvarez-Martinez, Marisol
• Luisier, Raphaëlle
• Cox, Luke S
• Sodenkamp, Jan
• Hosking, Caroline
• Pérez-Mazliah, Damián
• Whicher, Charlotte
• Kannan, Yashaswini
• Potempa, Krzysztof
• Wu, Xuemei
• Bhaw, Leena
• Wende, Hagen
• Sieweke, Michael H
• Elgar, Greg
• Wilson, Mark
• Briscoe, James
• Metzis, Vicki
• Langhorne, Jean
• Luscombe, Nicholas M
• O'Garra, Anne

Titel

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

Ist Teil von

• Nature immunology, 2018-05, Vol.19 (5), p.497

Ort / Verlag

United States

Erscheinungsjahr

2018

Link zum Volltext

Beschreibungen/Notizen

• 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 1 subset of helper T cells (malaria), T 2 cells (allergy) and T 17 cells (autoimmunity) in vivo. Although mice with c-Maf deficiency targeted to T cells showed greater pathology in T 1 and T 2 responses, T 17 cell-mediated pathology was reduced in this context, with an accompanying decrease in T 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 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.