Acetylcholine ameliorates colitis by promoting IL-10 secretion of monocytic myeloid-derived suppressor cells through the nAChR/ERK pathway
| Autor: | Feifei Luo, Zhongguang Luo, Lin Chen, Huan Song, Haoshu Cui, Bangting Wang, Yao Liu, Yufei Zhang, Hao Wu, Wanwei Zheng, Jun Zhang, Wenshuai Li, Yiwei Chu, Jie Liu, Yuedi Wang |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Inflammation Receptors Nicotinic Enteric Nervous System Monocytes Choline O-Acetyltransferase Mice 03 medical and health sciences 0302 clinical medicine Animals Humans Medicine Colitis Extracellular Signal-Regulated MAP Kinases Neurons Multidisciplinary business.industry Myeloid-Derived Suppressor Cells Biological Sciences Inflammatory Bowel Diseases medicine.disease Choline acetyltransferase Acetylcholine digestive system diseases Interleukin-10 Mice Inbred C57BL 030104 developmental biology 030220 oncology & carcinogenesis Cancer research Myeloid-derived Suppressor Cell Cholinergic Female Enteric nervous system medicine.symptom business medicine.drug |
| Zdroj: | Proc Natl Acad Sci U S A |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.2017762118 |
| Popis: | The alteration of the enteric nervous system (ENS) and its role in neuroimmune modulation remain obscure in the pathogenesis of inflammatory bowel diseases (IBDs). Here, by using the xCell tool and the latest immunolabeling-enabled three-dimensional (3D) imaging of solvent-cleared organs technique, we found severe pathological damage of the entire ENS and decreased expression of choline acetyltransferase (ChAT) in IBD patients. As a result, acetylcholine (ACh), a major neurotransmitter of the nervous system synthesized by ChAT, was greatly reduced in colon tissues of both IBD patients and colitis mice. Importantly, administration of ACh via enema remarkably ameliorated colitis, which was proved to be directly dependent on monocytic myeloid-derived suppressor cells (M-MDSCs). Furthermore, ACh was demonstrated to promote interleukin-10 secretion of M-MDSCs and suppress the inflammation through activating the nAChR/ERK pathway. The present data reveal that the cholinergic signaling pathway in the ENS is impaired during colitis and uncover an ACh-MDSCs neuroimmune regulatory pathway, which may offer promising therapeutic strategies for IBDs. |
| Databáze: | OpenAIRE |
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