2. Academic Validation
  3. Oxytocin signalling in dendritic cells regulates immune tolerance in the intestine and alleviates DSS-induced colitis

Oxytocin signalling in dendritic cells regulates immune tolerance in the intestine and alleviates DSS-induced colitis

  • Clin Sci (Lond). 2021 Feb 26;135(4):597-611. doi: 10.1042/CS20201438.
Dandan Dou 1 2,  Jinghui Liang 1,  Xiangyu Zhai 3,  Guosheng Li 4,  Hongjuan Wang 5,  Liying Han 6 7,  Lin Lin 8,  Yifei Ren 1,  Shilian Liu 2,  Chuanyong Liu 1,  Wei Guo 9,  Jingxin Li 1
Affiliations

Affiliations

  • 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.
PMID: 33564880 DOI: 10.1042/CS20201438
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.

Keywords

Dendritic cells; Oxytocin; Pi3K/AKT pathway; Ulcerative Colitis; helper T cells.

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