Th17 mediated recurrence of virus-induced immunopathology following discontinued FTY720 treatment (105.10)

Abstract

Abstract In this report we show that the anti-inflammatory effect of FTY720 is lost on the discontinuation of treatment in Herpes Simplex Virus (HSV-I) induced ocular inflammation. The lesions developed after FTY720 treatment withdrawals were characterized by the predominance of Th17 cells over Th1 cells. Th17 but not Th1 cells expressed higher levels of surface CD103, an integrin that permits migration to inflammatory sites. Furthermore, we demonstrate that CD4+ T cells isolated from FTY720 treated but uninfected mice could be efficiently polarized towards Th17 and Treg but to a lesser extent towards Th1 phenotype. The hyper acute emergence of inflammation in FTY720 treated animals could be slowed down in IL-17RKO mice and upon administration of neutralizing antibody for IL-6, a proinflammatory cytokine involved in the generation of Th17 cells. These results suggested that approaches such as neutralization of proinflammatory cytokines might be considered along with FTY720 if interruption of the therapy is required to achieve the anti-inflammatory effects of the drug.