Activation of the transcription factor c-Maf in T cells is dependent on the CARMA1-IKK? signaling cascade.

ABSTRACT: The proto-oncogene c-Maf is a transcription factor that plays a critical role in the differentiation of various T helper (T(H)) cell subsets. The amount of c-Maf increases after stimulation of the T cell receptor (TCR), which results in the production of multiple cytokines. We showed that two essential regulators of the transcription factor nuclear factor ?B (NF-?B), the scaffold protein CARMA1 and the kinase IKK? [inhibitor of NF-?B (I?B) kinase ?], are also critical for the activation of c-Maf. Although CARMA1 deficiency did not affect the TCR-dependent increase in c-Maf abundance in T cells, CARMA1-dependent activation of the IKK complex was required for the nuclear translocation of c-Maf and its binding to the promoters of its target genes. Consistent with a role for c-Maf in the development of T follicular helper (T(FH)) cells, which provide help to B cells in the germinal centers of the spleen, CARMA1- or IKK?-deficient mice immunized with peptide antigen had defects in the generation of T(FH) cells, formation of germinal centers, and production of antigen-specific antibodies. Together, these data suggest a mechanism by which c-Maf is regulated during T cell activation and differentiation.

SUBMITTER: Blonska M 

PROVIDER: S-EPMC5762115 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature