New paper by the Sallusto lab published in Nature Immunology

on September 10, 2018

T helper lymphocytes that produce IL-17 (T_H17 cells) are pivotal in protection against extracellular bacteria and fungi. They exert this function by recruiting neutrophils and by secreting a wide range of pro-inflammatory cytokines and effector molecules. T_H17 cells can also induce severe tissue damage and chronic inflammation, eventually leading to autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis and Crohn’s disease. In the study entitled “An immunoregulatory and tissue-residency program modulated by c-MAF in human T_H17 cells” and published in Nature Immunology, the research team led by prof. Federica Sallusto characterized two subsets of human T_H17 cells that could be distinguished on the basis of their expression of the anti-inflammatory cytokine IL-10. IL-10-positive T_H17 cells expressed a variety of genes encoding immunoregulatory molecules, as well as genes whose expression is characteristic of tissue-resident T cells. In contrast, IL-10-negative T_H17 cells possessed a pro-inflammatory gene-expression profile and upregulated expression of homing receptors that guide recirculation from tissues to blood. The data further demonstrated that the immunoregulatory and tissue-residency program of IL-10-positive T_H17 cells is modulated by c-MAF, which binds to a large number of regulatory regions, acting as a transcriptional co-activator or co-repressor in a context dependent manner. The characterization of human T_H17 cells with programmed opposing fates sets the stage for studying their physiological functions and opens new possibilities for therapeutic interventions in autoimmune pathologies.

Immuno-regulatory and pro-inflammatory human TH17 cells

The work was supported by the European Research Council, the Swiss National Science Foundation and the National Institutes of Health.

Article

An immunoregulatory and tissue-residency program modulated by c-MAF in human T_H17 cells

Dominik Aschenbrenner, Mathilde Foglierini, David Jarrossay, Dan Hu, Howard L. Weiner, Vijay K. Kuchroo, Antonio Lanzavecchia, Samuele Notarbartolo^* and Federica Sallusto^*.

^*equal contribution

Nature Immunology, DOI: 10.1038/s41590-018-0200-5