c-Maf regulates the plasticity of group 3 innate lymphoid cells by restraining the type 1 program.

Published

Journal Article

CCR6- group 3 innate lymphoid cells (ILC3s) are mediators of intestinal immunity and barrier function that possess the capacity to acquire type 1 effector features and fully convert into ILC1s. The molecular mechanisms governing such plasticity are undefined. Here, we identified c-Maf as an essential regulator of ILC3 homeostasis and plasticity that limits physiological ILC1 conversion. Phenotypic analysis of effector status in Maf-deficient CCR6- ILC3s, coupled with evaluation of global changes in transcriptome, chromatin accessibility, and transcription factor motif enrichment, revealed that c-Maf enforces ILC3 identity. c-Maf promoted ILC3 accessibility and supported RORγt activity and expression of type 3 effector genes. Conversely, c-Maf antagonized type 1 programming, largely through restraint of T-bet expression and function. Mapping of the dynamic changes in chromatin landscape accompanying CCR6- ILC3 development and ILC1 conversion solidified c-Maf as a gatekeeper of type 1 regulatory transformation and a controller of ILC3 fate.

Full Text

Duke Authors

Cited Authors

  • Parker, ME; Barrera, A; Wheaton, JD; Zuberbuehler, MK; Allan, DSJ; Carlyle, JR; Reddy, TE; Ciofani, M

Published Date

  • January 6, 2020

Published In

Volume / Issue

  • 217 / 1

PubMed ID

  • 31570496

Pubmed Central ID

  • 31570496

Electronic International Standard Serial Number (EISSN)

  • 1540-9538

Digital Object Identifier (DOI)

  • 10.1084/jem.20191030

Language

  • eng

Conference Location

  • United States