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

Autor:	Parker ME; Department of Immunology, Duke University Medical Center, Durham, NC., Barrera A; Center for Genomic and Computational Biology, Duke University Medical School, Durham, NC.; Department of Biostatistics and Bioinformatics, Duke University Medical School, Durham, NC., Wheaton JD; Department of Immunology, Duke University Medical Center, Durham, NC., Zuberbuehler MK; Department of Immunology, Duke University Medical Center, Durham, NC., Allan DSJ; Department of Immunology, University of Toronto, Toronto, Canada., Carlyle JR; Department of Immunology, University of Toronto, Toronto, Canada., Reddy TE; Center for Genomic and Computational Biology, Duke University Medical School, Durham, NC.; Department of Biostatistics and Bioinformatics, Duke University Medical School, Durham, NC., Ciofani M; Department of Immunology, Duke University Medical Center, Durham, NC.
Jazyk:	angličtina
Zdroj:	The Journal of experimental medicine [J Exp Med] 2020 Jan 06; Vol. 217 (1).
DOI:	10.1084/jem.20191030
Abstrakt:	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. (© 2019 Parker et al.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu