New Nature Immunology Paper by the Sallusto Lab
An immunoregulatory and tissue-residency program modulated by c-MAF in human TH17 cells
Dominik Aschenbrenner, Mathilde Foglierini, David Jarrossay, Dan Hu, Howard L. Weiner, Vijay K. Kuchroo, Antonio Lanzavecchia, Samuele Notarbartolo and Federica Sallusto
Nat Immunol. 2018 Sep 10. doi: 10.1038/s41590-018-0200-5. [Epub ahead of print]
Different types of effector and memory T lymphocytes are induced and maintained in protective or pathological immune responses. Here we characterized two human CD4+ TH17 helper cell subsets that, in the recently activated state, could be distinguished on the basis of their expression of the anti-inflammatory cytokine IL-10. IL-10+ TH17 cells upregulated a variety of genes encoding immunoregulatory molecules, as well as genes whose expression is characteristic of tissue-resident T cells. In contrast, IL-10– TH17 cells maintained a pro-inflammatory gene-expression profile and upregulated the expression of homing receptors that guide recirculation from tissues to blood. Expression of the transcription factor c-MAF was selectively upregulated in IL-10+ TH17 cells, and it was bound to a large set of enhancer-like regions and modulated the immunoregulatory and tissue-residency programs. Our results identify c-MAF as a relevant factor that drives two highly divergent post-activation fates of human TH17 cells and provide a framework with which to investigate the role of these cells in physiology and immunopathology.