Enhanced ICOS-L expression on DC in IL-10 deficiency and its impact on T cell subsets in respiratory tract infection (P1332)

Abstract

Abstract Association of ICOS-L expression and IL-10 production by dendritic cells (DCs) has been commonly found in infectious disease models. The DCs with higher ICOSL expression and IL-10 production are reportedly more efficient in inducing regulatory T cells (Treg). To test whether IL-10 production and ICOS-L expression has a causal relationship, we examined ICOS-L expression by DC in IL-10 knockout (KO) mice in Chlamydia muridarum (Cm) lung infection. Moreover, we examined the development of T cell subsets, including Treg, Th17 and Th1 cell, in the condition of IL-10 deficiency and its relationship with ICOSL/ICOS signaling following infection. Surprisingly, we found that the IL-10 KO mice exhibited significantly higher ICOS-L expression by DCs. And the IL-10 KO mice showed lower Treg but higher Th17 and Th1 responses. Further analysis of Th17 and Th1 cells showed that only the Th17 response was dependent on ICOS signaling. Consistently, most of the Th17 cells were ICOS+, while most of the Th1 cells were ICOS- in the infected mice. The data suggest that ICOSL expression is independent of IL-10 production and that ICOS-L expression on DC in the presence or absence of IL-10 co-stimulation may respectively promoting Treg or Th17 response, without significant impact on Th1. The data also suggest that the enhanced protection in IL-10 KO mice may be due to the synergy of Th17 and Th1 responses.