PMID- 35125962 OWN - NLM STAT- MEDLINE DCOM- 20220331 LR - 20220501 IS - 1466-1861 (Electronic) IS - 0962-9351 (Print) IS - 0962-9351 (Linking) VI - 2022 DP - 2022 TI - Role of Cholinergic Anti-Inflammatory Pathway in Protecting Sepsis-Induced Acute Lung Injury through Regulation of the Conventional Dendritic Cells. PG - 1474891 LID - 10.1155/2022/1474891 [doi] LID - 1474891 AB - BACKGROUND: The cholinergic anti-inflammatory pathway connects the immune response system and the nervous system via the vagus nerve. The key regulatory receptor is the alpha7-subtype of the nicotinic acetylcholine receptor (alpha7nAChR). Cholinergic anti-inflammatory pathway has been proved to be effective in suppressing the inflammation responses in acute lung injury (ALI). Dendritic cells (DCs), the important antigen-presenting cells, also express the alpha7nAChR. Past studies have indicated that reducing the quantity of mature conventional DCs and inhibiting the maturation of pulmonary DCs may prove effective for the treatment of ALI. However, the effects of cholinergic anti-inflammatory pathway on maturation, function, and quantity of DCs and conventional DCs in ALI remain unclear. OBJECTIVE: It was hypothesized that cholinergic anti-inflammatory pathway may inhibit the inflammatory response of ALI by regulating maturation, phenotype, and quantity of DCs and conventional DCs. METHODS: GTS-21 (GTS-21 dihydrochloride), an alpha7nAchR agonist, was prophylactically administered in sepsis-induced ALI mouse model and LPS-primed bone marrow-derived dendritic cells. The effects of GTS-21 were observed with respect to maturation, phenotype, and quantity of DCs, conventional DCs, and conventional DCs2 (type 2 conventional DCs) and the release of DC-related proinflammatory cytokines in vivo and in vitro. RESULTS: The results of the present study revealed that GTS-21 treatment decreased the maturation of DCs and the production of DC-related proinflammatory cytokines in vitro and in sepsis-induced ALI mouse model; it reduced the quantity of CD11c(+)MHCII(+) conventional DCs and CD11c(+)CD11b(+) conventional DCs2 in vivo experiment. CONCLUSIONS: Cholinergic anti-inflammatory pathway contributes to the reduction in the inflammatory response in ALI by regulating maturation, phenotype, and quantity of DCs, conventional DCs, and conventional DCs2. CI - Copyright (c) 2022 Ruiting Li et al. FAU - Li, Ruiting AU - Li R AUID- ORCID: 0000-0001-8041-1050 AD - Department of Critical Care Medicine, Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China. FAU - Hu, Xuemei AU - Hu X AD - Department of Nephrology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei Province 442000, China. FAU - Chen, Huibin AU - Chen H AD - Department of Critical Care Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei Province 442000, China. FAU - Zhao, Yue AU - Zhao Y AD - Department of Critical Care Medicine, Jin Yin-tan Hospital, Wuhan, Hubei 430048, China. FAU - Gao, Xuehui AU - Gao X AD - Department of Critical Care Medicine, Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China. FAU - Yuan, Yin AU - Yuan Y AD - Department of Critical Care Medicine, Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China. FAU - Guo, Huiling AU - Guo H AD - Department of Critical Care Medicine, Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China. FAU - Huang, Haiyan AU - Huang H AUID- ORCID: 0000-0002-3795-0195 AD - Department of Critical Care Medicine, Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China. FAU - Zou, Xiaojing AU - Zou X AUID- ORCID: 0000-0002-7849-4958 AD - Department of Critical Care Medicine, Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China. FAU - Qi, Hong AU - Qi H AUID- ORCID: 0000-0002-6811-9644 AD - Department of Critical Care Medicine, Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China. FAU - Liu, Hong AU - Liu H AUID- ORCID: 0000-0001-8331-3405 AD - Department of Critical Care Medicine, Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China. FAU - Shang, You AU - Shang Y AUID- ORCID: 0000-0003-4097-6131 AD - Department of Critical Care Medicine, Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China. LA - eng PT - Journal Article DEP - 20220127 PL - United States TA - Mediators Inflamm JT - Mediators of inflammation JID - 9209001 RN - 0 (Lipopolysaccharides) SB - IM MH - *Acute Lung Injury/metabolism MH - Animals MH - Dendritic Cells/metabolism MH - Lipopolysaccharides/metabolism/pharmacology MH - Mice MH - Neuroimmunomodulation MH - *Sepsis/metabolism PMC - PMC8813293 COIS- The authors declare that they have no conflicts of interest. EDAT- 2022/02/08 06:00 MHDA- 2022/04/01 06:00 PMCR- 2022/01/27 CRDT- 2022/02/07 05:28 PHST- 2021/10/02 00:00 [received] PHST- 2022/01/03 00:00 [revised] PHST- 2022/01/06 00:00 [accepted] PHST- 2022/02/07 05:28 [entrez] PHST- 2022/02/08 06:00 [pubmed] PHST- 2022/04/01 06:00 [medline] PHST- 2022/01/27 00:00 [pmc-release] AID - 10.1155/2022/1474891 [doi] PST - epublish SO - Mediators Inflamm. 2022 Jan 27;2022:1474891. doi: 10.1155/2022/1474891. eCollection 2022.