Gpr174 knockout alleviates DSS-induced colitis via regulating the immune function of dendritic cells

Dysfunction of the immune system would disturb the intestinal homeostasis and lead to inflammatory bowel disease (IBD). Dendritic cells (DCs) help maintain intestinal homeostasis and immediately respond to pathogens or injuries once the mucosa barriers are destroyed during IBD. GPR174 is an essential regulator of immunity which widely expressed in most immune cells including DCs. However, the role of GPR174 in regulating the immune function of DC in colitis has not been investigated. This study established the colitis model by using dextran sodium sulfate (DSS) orally. Data of weight, length of colon, disease activity index (DAI) and macroscopic scores were collected. Mean fluorescence intensity (MFI) of CD80, CD86, CD40, major histocompatibility complex-II (MHC-II), and T cells labelled with carboxifluorescein diacetate succinimidyl ester (CFSE), infiltrations of T cells, and DCs were detected by flow cytometry. The expression of cytokines (tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-10 (IL-10), interferon-gamma (IFN-gamma), interleukin -4 (IL-4) and GPR174 mRNA were measured by Elisa, quantitative polymerase chain reaction (qPCR), and immunofluorescence. RNA of BMDCs was extracted for sequencing. Adoptive transfer of BMDCs was administrated intravenously. And Our study indicated that Gpr174 was involved in the pathogenesis of IBD by regulating the maturation of the dendritic cells to maintain immune homeostasis. TNF-alpha signaling pathway, leukocyte transendothelial migration, and Th1/Th2 cell differentiation pathways may be involved.