The transcription factor c-Maf is essential for the commitment of IL-17-producing γδ T cells.

Published

Journal Article

γδ T cells that produce the cytokine IL-17 (Tγδ17 cells) are innate-like mediators of immunity that undergo effector programming in the thymus. While regulators of Tγδ17 specialization restricted to various Vγ subsets are known, a commitment factor essential to all Tγδ17 cells has remained undefined. In this study, we identified the transcription factor c-Maf as a universal regulator of Tγδ17 cell differentiation and maintenance. Maf deficiency caused an absolute lineage block at the immature CD24+CD45RBlo γδ thymocyte stage, which revealed a critical checkpoint in the acquisition of effector functions. Here, c-Maf enforced Tγδ17 cell identity by promoting chromatin accessibility and expression of key type 17 program genes, notably Rorc and Blk, while antagonizing the transcription factor TCF1, which promotes interferon-γ-producing γδ T cells (Tγδ1 cells). Furthermore, γδ T cell antigen receptor (γδTCR) signal strength tuned c-Maf expression, which indicates that c-Maf is a core node that connects γδTCR signals to Tγδ17 cell transcriptional programming.

Full Text

Duke Authors

Cited Authors

  • Zuberbuehler, MK; Parker, ME; Wheaton, JD; Espinosa, JR; Salzler, HR; Park, E; Ciofani, M

Published Date

  • January 2019

Published In

Volume / Issue

  • 20 / 1

Start / End Page

  • 73 - 85

PubMed ID

  • 30538336

Pubmed Central ID

  • 30538336

Electronic International Standard Serial Number (EISSN)

  • 1529-2916

Digital Object Identifier (DOI)

  • 10.1038/s41590-018-0274-0

Language

  • eng

Conference Location

  • United States