Either a Th 17 or a Th 1 eff ector response can drive autoimmunity : conditions of disease induction aff ect dominant eff ector category Dror

JEM © The Rockefeller University Press $30.00 Vol. 205, No. 4, April 14, 2008 799-810 www.jem.org/cgi/doi/ 799 10.1084/jem.20071258 IL-23 is a recently described member of the IL-12 family. Both cytokines share a common p40 subunit, but IL-23 has a unique p19 subunit whereas IL-12 uses a p35 subunit ( 1 ). IL-12 and IL-23 promote overlapping as well as distinct cellular immune functions. Whereas IL – 12 is well known for promoting the IFN– producing Th1 eff ector phenotype in the adaptive response, IL-23 is reported to promote IL-17 – producing eff ector T cells that constitute a separate lineage from Th1 and Th2 and have been appropriately dubbed “ Th17. ” Recent studies have suggested that these cells may have an important role in cell-mediated autoimmune infl ammatory diseases. Experimental autoimmune uveitis (EAU) serves as a model for several human ocular diseases of suspected autoimmune etiology ( 2 – 4 ). EAU is elicited by immunization with retinal antigens (Ags) or their fragments ( 5 ), or by adoptive transfer of retinal Ag-specifi c CD4 + T cells between syngeneic rodents ( 6, 7 ). Published data provide evidence that a Th1-dominant response and the Th1 eff ector cell are critical for EAU development and that endogenous IL-12 is needed for EAU induction and its full expression ( 8, 9 ). However, susceptibility to EAU of IFN – defi cient (GKO) mice, exacerbation of EAU by neutralization of endogenous IFN , and the protective eff ects of high systemic IFN in WT mice ( 10 – 12 ) were in apparent paradox with this notion. The requirement for IL-12 – mediated IFN and Th1 responses in autoimmune infl ammation has recently been questioned by several studies in other disease models. Mice defi cient in IFN , IFN R, IL-12R  2, and the IL12p35 chain were highly susceptible to experimental autoimmune encephalomyelitis (EAE) and collagen-induced arthritis (CIA) ( 13 – 15 ). In contrast, IL-23 and the IL-17 – producing eff ector T cell whose diff erentiation and maintenance CORRESPONDENCE Rachel R. Caspi: [email protected]