Dandan Dou1,2, Jinghui Liang1, Xiangyu Zhai3, Guosheng Li4, Hongjuan Wang5, Liying Han6,7, Lin Lin8, Yifei Ren1, Shilian Liu2, Chuanyong Liu1, Wei Guo9, Jingxin Li1. 1. Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China. 2. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China. 3. Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, China. 4. Department of Hematology, Qilu Hospital of Shandong University, Jinan 250012, China. 5. Department of Gastroenterology, Second Hospital, Shandong University, Jinan 250000, China. 6. College of Life Science, Shandong Normal University, Jinan 250014, China. 7. State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266000, China. 8. Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan 250012, China. 9. Department of Colorectal Surgery, Qilu Hospital of Shandong University, Jinan 250012, China.
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 (OXTRflox/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.
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 (OXTRflox/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 colitismice 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.
Authors: Samar O El-Ganainy; Omar A Soliman; Aya A Ghazy; Maram Allam; Aya I Elbahnasi; Amira M Mansour; Mennatallah A Gowayed Journal: Neurochem Res Date: 2022-05-20 Impact factor: 4.414