A Novel Role of Smyd2 in Inflammatory Bowel Disease by Orchestrating Macrophage Polarization

Inflammatory bowel disease (IBD) is a chronic condition caused by an abnormal immune response to gut microflora that leads to inflammation in the gastrointestinal tract. Intestinal macrophages are emerging as key players in IBD pathogenesis. Especially, inflammatory M1 macrophages contribute to the onset and progression of IBD, whereas immunosuppressive M2 macrophages show protective activity against IBD. Orchestrating macrophage polarization is considered a potential therapeutic strategy for IBD, but it needs a better understanding of the mechanism underlying macrophage polarization in IBD. Here, we collected specimens from patients with IBD and established a dextran sodium sulfate (DSS)-induced murine colitis model to mimic human IBD. We observed that Smyd2 expression was reduced in both patients with IBD and mice with experimental colitis, and Smyd2 predominantly localized in macrophages. Then, we isolated mouse peritoneal macrophages and overexpressed Smyd2 in macrophages. We found that the overexpression of Smyd2 significantly repressed lipopolysaccharide (LPS)-induced M1 polarization but enhanced interleukin-4 (IL-4)-induced M2 polarization. Furthermore, overexpression of Smyd2 suppressed M1 polarization but promoted M2 polarization in mice with colitis. Collectively, Smyd2 orchestrates macrophage polarization in IBD. Our findings shed novel insight into the mechanism of macrophage polarization in IBD and suggest Smyd2 as a potential therapeutic target and prognosis biomarker for IBD.