Georgina Xanthou and colleagues recently published a study in PNAS

Pathogenic Th17 cells are critical drivers of autoimmune neuroinflammation in multiple sclerosis (MS). We report that administration of the cytokine activin-A ameliorated disease severity in an animal MS model and attenuated CNS neuroinflammation associated with decreased pathogenic Th17 responses. Whole-genome profiling and functional studies revealed that activin-A upregulated the antiinflammatory CD73 and CD39 ectonucleotidases and this was essential for the suppression of the pathogenic signature and encephalitogenic functions of Th17 cells. Mechanistically, activin-A signaling increased antiinflammatory gene expression through activation of the transcription factors AhR, STAT3, and c-Maf and inhibited pathogenic Th17 programs through down-regulation of the metabolic sensor, Hif1-α, and other inflammatory proteins. Of clinical relevance, we show that activin-A restrained pathogenic human Th17 cell responses in MS patients.

Activin-A limits Th17 pathogenicity and autoimmune neuroinflammation via CD39 and CD73 ectonucleotidases and Hif1-α–dependent pathways

Ioannis Morianos, Aikaterini I. Trochoutsou, Gina Papadopoulou, Maria Semitekolou, Aggelos Banos, Dimitris Konstantopoulos, Antigoni Manousopoulou, Maria Kapasa, Ping Wei, Brett Lomenick, Elise Belaidi, Themis Kalamatas, Klinta Karageorgiou, Triantafyllos Doskas, Federica Sallusto, Fan Pan, Spiros D. Garbis, Francisco J. Quintana, and Georgina Xanthou. PNAS first published May 14, 2020 https://doi.org/10.1073/pnas.1918196117

Pubmed