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Using an unbiased chemical biology approach, we identified a novel role for the dual specificity tyrosine-phosphorylation-regulated kinase DYRK1A in regulating this balance. Inhibition of DYRK1A enhances Treg differentiation and impairs Th17 differentiation without affecting known pathways of Treg\/Th17 differentiation. Thus, DYRK1A represents a novel mechanistic node at the branch point between commitment to either Treg or Th17 lineages. Importantly, both Treg cells generated using the DYRK1A inhibitor harmine and direct administration of harmine itself potently attenuate inflammation in multiple experimental models of systemic autoimmunity and mucosal inflammation. Our results identify DYRK1A as a physiologically relevant regulator of Treg cell differentiation and suggest a broader role for other DYRK family members in immune homeostasis. These results are discussed in the context of human diseases associated with dysregulated DYRK activity.<\/jats:p>","DOI":"10.7554\/elife.05920","type":"journal-article","created":{"date-parts":[[2015,5,22]],"date-time":"2015-05-22T05:57:28Z","timestamp":1432274248000},"source":"Crossref","is-referenced-by-count":67,"title":["The kinase DYRK1A reciprocally regulates the differentiation of Th17 and regulatory T cells"],"prefix":"10.7554","volume":"4","author":[{"given":"Bernard","family":"Khor","sequence":"first","affiliation":[{"name":"Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Harvard Medical School, Boston, United States"},{"name":"Center for Computational and Integrative Biology, Massachusetts General Hospital, Harvard Medical School, Boston, United States"},{"name":"Broad Institute of MIT and Harvard, Cambridge, United States"},{"name":"Pathology Service, Massachusetts General Hospital, Boston, United 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