Oxytocin signalling in dendritic cells regulates immune tolerance in the intestine and alleviates DSS-induced colitis. Issue 4 (26th February 2021)

• Record Type: Journal Article
• Authors: Dou, Dandan; Liang, Jinghui; Zhai, Xiangyu; Li, Guosheng; Wang, Hongjuan; Han, Liying; Lin, Lin; Ren, Yifei; Liu, Shilian; Liu, Chuanyong; Guo, Wei; Li, Jingxin
• Is Part Of: Clinical science. Volume 135:Issue 4(2021)
• Page Start: 597
• Page End: 611
• Publication Date: 2021-02-26
• Subjects: Dendritic cells -- helper T cells -- Oxytocin -- Pi3K/AKT pathway -- Ulcerative Colitis; Medicine -- Periodicals; Biochemistry -- Periodicals; 616
• DOI: 10.1042/CS20201438
• Languages: English
• ISSNs: 0143-5221

Abstract

Abstract: Background: Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) that is associated with immune dysfunction. Recent studies have indicated that the neurosecretory hormone oxytocin (OXT) has been proven to alleviate experimental colitis. Methods: We investigated the role of OXT/OXT receptor (OXTR) signalling in dendritic cells (DCs) using mice with specific OXTR deletion in CD11c + cells (OXTR flox/flox ×CD11c-cre mice) and a dextran sulfate sodium (DSS)-induced colitis model. Results: The level of OXT was abnormal in the serum or colon tissue of DSS-induced colitis mice or the plasma of UC patients. Both bone marrow-derived DCs (BMDCs) and lamina propria DCs (LPDCs) express OXTR. Knocking out OXTR in DCs exacerbated DSS-induced acute and chronic colitis in mice. In contrast, the injection of OXT-pretreated DCs significantly ameliorated colitis. Mechanistically, OXT prevented DC maturation through the phosphatidylinositol 4, 5-bisphosphate 3-kinase (Pi3K)/AKT pathway and promoted phagocytosis, adhesion and cytokine modulation in DCs. Furthermore, OXT pre-treated DCs prevent CD4 + T cells differentiation to T helper 1 (Th1) and Th17. Conclusions: Our results suggest that OXT-induced tolerogenic DCs efficiently protect against experimental colitis via Pi3K/AKT pathway. Our work provides evidence that the nervous system participates in the immune regulation of colitis by modulating DCs. Our findings suggest that generating ex vivo DCs pretreated with OXT opens new therapeutic perspectives for the treatment of UC in humans.