Th17 cell function and Th17-mediated autoimmune disease

© 2008 Pappu et al. The Rockefeller University Press $30.00 J. Exp. Med. Vol. 205 No. 5 1049-1062 www.jem.org/cgi/doi/ 1049 10.1084/jem.20071364 After activation, CD4 + Th cells diff erentiate into distinct eff ector subsets that are characterized by their unique cytokine expression and immunoregulatory function ( 1, 2 ). A novel Th subset — termed Th IL-17 , Th17, or infl ammatory Th — has been recently identifi ed as a distinct Th lineage that mediates tissue infl ammation ( 3 – 5 ). Th17 diff erentiation is initiated by TGFand IL-6 ( 4, 6, 7 ), and reinforced by IL-23 ( 8 ) and IL-21 ( 9 – 11 ), in which STAT3 and two orphan nuclear receptors, ROR and ROR , mediate the lineage specifi cation ( 8, 12 – 14 ). Despite rapid progress in understanding the molecular programs that govern Th17 diff erentiation, it is not clear how their proliferation, and ultimately function, are regulated in the context of immune responses and diseases. Th cell activation and diff erentiation requires not only the recognition of the antigen – MHC class II complex by the cognate TCR but also co-stimulatory signals. Previous experiments have indicated diff erential co-stimulatory regulation of Th1 and Th2 cell function ( 15 ). Over the past decade, our knowledge of how diff erent ligand – receptor pairing interactions contribute to T cell co-stimulation has been steadily expanded. Most of these pairs belong to either the B7-type molecules that bind CD28-like Ig superfamily receptors, or the TNF superfamily ligands that engage their receptor counterparts in the TNFR family ( 16 ). Although we have previously shown essential roles of CD28 and inducible co-stimulator in Th17 diff erentiation ( 17, 18 ), the functional contribution of TNF and TNFR family members in regulating Th17 cell function is poorly understood. CORRESPONDENCE Chen Dong: [email protected] OR Linda C. Burkly: [email protected]