Characterization of two activation-dependent divergent fates in human TH17 cells

Cellular Immunology Group, Institute for Research in Biomedicine (IRB) Bellinzona - (Switzerland)

4 th March 2019
Versione stampabile

Luogo: Povo 2 - aula B104
Orario: 15.30

Relatore: 

  • Samuele Notarbartolo

Cellular Immunology Group, Institute for Research in Biomedicine (IRB)

Bellinzona - (Switzerland)

Abstract:
Different types of effector and memory T lymphocytes are induced and maintained in protective or pathological immune responses. In this study we characterized two human CD4+ TH17 cell subsets that, in the recently activated state, could be distinguished on the basis of their expression of the anti-inflammatory cytokine IL-10. We showed that, in addition to IL-10, recently-activated IL-10+ TH17 cells upregulated a variety of immunoregulatory genes, as well as genes whose expression is characteristic of tissueresident T cells. In contrast, recently-activated IL-10– TH17 cells upregulated the expression of homing receptors that guide recirculation from tissues to blood, and maintained a proinflammatory gene expression profile that correlated with the transcriptional footprint of biopsies from patients with Crohn’s disease and rheumatoid arthritis, two TH17-mediated autoimmune diseases. We demonstrated that the transcription factor c-MAF was selectively upregulated in recently-activated IL-10+ TH17 cells, it was bound to a large set of enhancerlike 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 to investigate the role of these cells in physiology and immunopathology.