The influence of CD206 in colonic macrophage to colorectal carcinogenesis

Abstract

CD206 also known as MRC1, is C-type lectin receptor that expressed mainly on tissue macrophage and dendritic cell, plays an important role in immune homeostasis through endocytosis. It is well known as a marker of alternatively activated or immune regulatory macrophage. Usually, high level of CD206 expression is known to indicate poor prognosis in various solid cancers, but other cases that induce anti-cancer immunity have been reported, so its role is ambiguous. In particular, the role of CD206 or unique signaling in colorectal carcinogenesis have not been clarified. In this study, a colitis-associated colorectal cancer model was induced by AOM/DSS to confirm the difference in tumorigenesis between WT and CD206 deficient groups. Also, the effect and mechanism of CD206 on colorectal cancer were confirmed through immunological analysis. When colon macrophage subset of littermate control and CD206 deficient mice were analyzed in steady and inflammatory state, The CD11b+ CX3CR1high subset, which has immunoregulatory characteristic, significantly decreased in CD206 deficient mice. But, CD11b+ CX3CR1-/int subset, which has immunogenic characteristic, was increased. In AOM/DSS results, increased tumor nodules in colon were observed in the CD206 deficient group. In addition, inflammatory mediators secreted by tissues and macrophages increased more than WT group. It is expected that difference in colonic macrophage subsets due to deficiency of CD206 may affect the development of early colorectal carcinogenesis. Therefore, CD206 can act as protective role against to development of colitis-associated colorectal carcinogenesis. _x000D_ <br>Keywords: CD206(MRC1), macrophage, AOM/DSS (azoxymethane/dextran sodium sulfate), colorectal carcinogenesis, inflammation