Abnormal innate immune response and Th1/Th17 induction in murine and human inflammatory bowel diseases (96.22)

Abstract

Abstract Recently, a lot of papers concerning IL-23/17 axis in some inflammatory conditions have been reported. IL-12p70/IL-23 are considered to regulate Th1/Th17 reciprocally in vitro, however, in vivo, both IFN-γ and IL-17 were reported to be upregulated in murine and human inflammatory bowel diseases (IBD). We previously reported the excess production of IL-12 and IL-23 by innate immune system in IL-10 deficient mice (Kamada N et al. J Immunol 2005; 175(10)) and in the present study, we have tried to unravel the role of innate immune system in induction of Th1/Th17 in murine colitis and human IBD. Colonic lamina propria CD4+ T cells of colitis mice were examined by intracellular cytokine staining and ELISA, and showed the upregulated production of both IFN- γ and IL-17. Similarly, these cytokines from CD4+ cells isolated from inflamed mucosa of human IBD are also increased in relation to upregulated IL-12/23. As expected, both macrophages and dendritic cells from IL-10 deficient mice produced larger amount of IL-12 and IL-23 than WT mice. Furthermore, macrophages and dendritic cells from IL-10 deficient mice could effectively stimulate both IFN- γ and IL-17 production in vitro. These results indicate that abnormal innate immune response stimulates both Th1 and Th17 simultaneously in murine and human inflammatory bowel disease.