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

Area of Science:

• Immunology
• Molecular Biology
• Genetics

Background:

• The transcription factor c-Maf is known to induce the anti-inflammatory cytokine IL-10 in CD4+ T cells in vitro.
• The comprehensive in vivo effects of c-Maf on diverse immune responses remain largely unknown.

Purpose of the Study:

• To investigate the global effects of c-Maf on various immune responses in vivo.
• To elucidate the c-Maf transcription-factor network and its regulatory roles in T cell subsets.

Main Methods:

• Utilized disease models for T helper 1 (malaria), T helper 2 (allergy), and T helper 17 (autoimmunity) responses in vivo.
• Employed bivariate genomic footprinting to map the c-Maf transcription-factor network.
• Assessed the impact of c-Maf deficiency on T cell populations and pathology.

Main Results:

• c-Maf deficiency exacerbated pathology in T helper 1 and T helper 2 responses but reduced pathology in T helper 17 responses.
• Identified c-Maf as a negative regulator of IL-2, with NFAT activity being enhanced.
• Demonstrated that c-Maf deficiency led to decreased RORγt expression, dependent on IL-2.

Conclusions:

• c-Maf acts as both a positive and negative regulator of cytokine gene expression.
• c-Maf exhibits context-specific effects, modulating immune responses for controlled yet effective outcomes.
• Findings reveal c-Maf's critical role in balancing different T cell-mediated immune pathways.