IL-23 promotes tumour incidence and growth
IL-23 promotes tumour incidence and growth
Nature 442, 461-465 (2006)
Speaker: 蔡政良 Time:15:10-16:00, Nov. 1, 2006
Commentator: 楊倍昌 老師 Place: Room 601
Abstract:
In recent years, the role of IL-23 in innate and adaptive immunity has been investigated considerably. According to previous studies, IL-23 and IL-12 play distinct and antagonistic roles in regulating innate immunity. IL-23 induces expression of IL-17 and IL-6 in ThIL-17 CD4+ T cells, resulting in chronic inflammation. In contrast, IL-12 promotes Th1 cells to produce IFN-g and other cytokines to activate immune cells to defense extrinsic pathogens or kill tumor cells1. Many studies have indicated that IL-23 is the critical cytokine for chronic inflammation and there is correlation between chronic inflammation and cancer2. Therefore, the authors hypothesized that IL-23 may play an important role in tumor incidence and growth and investigated the relationship between IL-23 and tumor. In this study, the authors used mice deficient in IL-12 and/or IL-23 (p35-/-, p19-/-, and p40-/- mice)and mice deficient in IL-12 and/or IL-23 receptor (IL-12Rb2-/-, IL-23R-/-, and IL-12Rb1-/- mice) to explore chemically carcinogen-induced and transplanted epithelial tumorigenesis. In IL-23 gene knockout mice, reduction of epithelial tumor incidence and down-regulation of IL-17, G-CSF, and MMP9 expression that linked to tumor growth were found. However, lower vessel density and infiltration of macrophages and neutrophils in the dermis were noted in IL-23 gene knockout mice compared with wild-type or IL-12 gene knockout mice. All of these results obtained from IL-23 gene knockout mice are opposite to those obtained from IL-12 gene knockout mice, further indicating the distinct roles of IL-23 and IL-12 in tumorigenesis. On the other hand, in IL-23 receptor gene knockout mice, there was apparent growth inhibition of transplanted epithelial tumor cells. In conclusion, these data demonstrate the significant role of IL-23 in tumor incidence and growth.
References:
1. Langrish, C. L. et al. IL-12 and IL-23: master regulators of innate and adaptive immunity. Immunol Rev 202, 96-105 (2004).
2. Coussens, L. M. & Werb, Z. Inflammation and cancer. Nature 420, 860-7 (2002).