Careful control of the differentiation of regulatory T cells (Treg cells) and the TH17 subset of helper T cells is required for balanced homeostatic and proinflammatory immune responses. In eLife, Xavier and colleagues use a chemical screen of more than 3,000 small molecule compounds to identify enhancers of Treg cell differentiation. One compound, the alkaloid harmine, enhances the in vitro and in vivo differentiation of Treg cells while at the same time impeding TH17 differentiation. Harmine alone is insufficient to generate Treg cells but instead seems to enhance signaling via transforming growth factor-β, known to be essential for the differentiation of this cell population. Harmine does not seem to act via any previously described pathway important for Treg cells; instead, it inhibits the kinase DYRK1A, and this action is essential for its Treg cell–enhancing effects. Precisely how DYRK1A controls the differentiation of Treg cells and TH17 cells remains to be determined.

eLife (22 May 2015) doi:10.7554/eLife.05920