IL-17A produced by peritoneal macrophages promote the accumulation and function of granulocytic myeloid-derived suppressor cells in the development of colitis-associated cancer

Abstract

It is widely acknowledged that a close relationship is between inflammation and colon cancer. Interleukin (IL)-17A and myeloid-derived suppressor cells (MDSCs) play an important role in the development of colitis-associated cancer (CAC). However, the precise changes of IL-17, MDSCs, and Th17 cells during the CAC progression have not been observed in the colorectal chronic inflammation-dependent tumor. In this study, we found the level of IL-17 was increased in pathogenic colon site during the early stage of CAC model. Further experiments showed the increased IL-17 was probably secreted by peritoneal macrophages when exposed to dextran sulfate sodium (DSS). In vitro, we found that IL-17 could enhance survival and suppressive function of granulocytic (G)-MDSCs, the subset associated with inflammation. With the development of CAC, the proportions of MDSCs and Th17 cells were continuously increased by the high level of IL-17 produced by macrophages. However, the increase of MDSCs was earlier and acuter than that of Th17 cells. Selective depletion of MDSCs not only slowed down CAC process but also significantly reduce Th17 cells in vivo. Thereafter, we demonstrated that in the development of CAC, IL-17 secreted by peritoneal macrophages could promote the accumulation of G-MDSCs, then the proportion of Th17 cells was increased, and finally promote the development of CAC.

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