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Institute for Research in Biomedicine
Istituto di Ricerca in Biomedicina

Via Vincenzo Vela 6 - CH-6500 Bellinzona
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New paper by the Sallusto lab published in Nature Immunology

on Monday, September 10, 2018

T helper lymphocytes that produce IL-17 (TH17 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. TH17 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 TH17 cells” and published in Nature Immunology, the research team led by prof. Federica Sallusto characterized two subsets of human TH17 cells that could be distinguished on the basis of their expression of the anti-inflammatory cytokine IL-10. IL-10-positive TH17 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 TH17 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 TH17 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 TH17 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 TH17 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