The transcription factor c-Maf is essential for the commitment of IL-17-producing γδ T cells.
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.
Duke Scholars
Altmetric Attention Stats
Dimensions Citation Stats
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- src-Family Kinases
- Thymocytes
- Th17 Cells
- Signal Transduction
- Receptors, Antigen, T-Cell, gamma-delta
- Proto-Oncogene Proteins c-maf
- Nuclear Receptor Subfamily 1, Group F, Member 3
- Mice, Knockout
- Mice, Inbred C57BL
- Mice
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- src-Family Kinases
- Thymocytes
- Th17 Cells
- Signal Transduction
- Receptors, Antigen, T-Cell, gamma-delta
- Proto-Oncogene Proteins c-maf
- Nuclear Receptor Subfamily 1, Group F, Member 3
- Mice, Knockout
- Mice, Inbred C57BL
- Mice