T helper 17 (Th17) cell plasticity contributes to both immunity and autoimmunity; however, the factors that control lineage flexibility are mostly unknown. Here we show the activator protein-1 (AP-1) factor JunB is an essential regulator of Th17 cell identity. JunB activates expression of Th17 lineage-specifying genes and coordinately represses genes controlling Th1 and regulatory T-cell fate. JunB supports Th17 cell identity by regulating key AP-1 complex constituents. In particular, JunB limits the expression of the subset repressor IRF8, and impedes access of JunD to regulatory regions of alternative effector loci. Although dispensable for homeostatic Th17 cell development, JunB is required for induction and maintenance of Th17 effector responses in the inflammatory contexts of both acute infection and chronic autoimmunity in mice. Through regulatory network analysis, we show that JunB is a core regulator of global transcriptional programs that promote Th17 cell identity and restrict alternative CD4+ T-cell potential.
16. We thank the entire Voyager team at NASA Headquarters and the Jet Propulsion Laboratory (JPL) for their support. We are especially grateful to R. Poynter for his invaluable assistance and support. We also thank E. Miner and J. Diner for their efforts to arrange the wideband coverage; J. Anderson, P. Jepsen, and G. Garneau for their assistance with the wideband data processing; C. Stembridge for his help in solving numerous problems; H. Bridge, J. Belcher, J. Scudder, and N. Ness for providing data in advance of publication and for their helpful discussions; and R. Anderson, R. West, L. Granroth, and R. Brechwald for carrying out the data reduction. The research at the University of Iowa was supported by NASA through contract 954013 with JPL, through grants NGL-16-001-002 and NGL-16-001-043 from NASA Headquarters, and by the Office of Naval Research. The research at TRW was supported by NASA through contract 954012 with JPL.
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