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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,7,2]]},"abstract":"<jats:p>\n                    The non-neural cholinergic system plays a critical role in regulating immune equilibrium and tissue homeostasis. While the expression of choline acetyltransferase (ChAT), the enzyme catalyzing acetylcholine biosynthesis, has been well documented in lymphocytes, its role in the myeloid compartment is less understood. Here, we identify a significant population of macrophages (M\u03d5s) expressing ChAT and synthesizing acetylcholine in the resolution phase of acute peritonitis. Using\n                    <jats:italic>Chat<\/jats:italic>\n                    -GFP reporter mice, we observed marked upregulation of ChAT in monocyte-derived small peritoneal M\u03d5s (SmPMs) in response to Toll-like receptor agonists and bacterial infections. These SmPMs, phenotypically and transcriptionally distinct from tissue-resident large peritoneal macrophages, up-regulated ChAT expression through a MyD88-dependent pathway involving MAPK signaling. Notably, this process was attenuated by the TRIF-dependent TLR signaling pathway, and our tests with a range of neurotransmitters and cytokines failed to induce a similar response. Functionally,\n                    <jats:italic>Chat<\/jats:italic>\n                    deficiency in M\u03d5s led to significantly decreased peritoneal acetylcholine levels, reduced efferocytosis of apoptotic neutrophils, and a delayed resolution of peritonitis, which were reversible with exogenous ACh supplementation. Intriguingly, despite B lymphocytes being a notable ChAT-expressing population within the peritoneal cavity,\n                    <jats:italic>Chat<\/jats:italic>\n                    deletion in B cells did not significantly alter the resolution process. Collectively, these findings underscore the crucial role of M\u03d5-derived acetylcholine in the resolution of inflammation and highlight the importance of the non-neuronal cholinergic system in immune regulation.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2402143121","type":"journal-article","created":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T13:35:51Z","timestamp":1719408951000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":16,"title":["Cholinergic macrophages promote the resolution of peritoneal inflammation"],"prefix":"10.1073","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8415-5699","authenticated-orcid":false,"given":"Shufeng","family":"Luo","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou 510060, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3995-8921","authenticated-orcid":false,"given":"Huiling","family":"Lin","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Pharmaceutical Functional Genes, Ministry of Education Key Laboratory of Gene Function and Regulation, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9593-293X","authenticated-orcid":false,"given":"Chong","family":"Wu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Pharmaceutical Functional Genes, Ministry of Education Key Laboratory of Gene Function and Regulation, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8866-6437","authenticated-orcid":false,"given":"Lan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Pharmaceutical Functional Genes, Ministry of Education Key Laboratory of Gene Function and Regulation, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaomin","family":"Hua","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou 510060, People\u2019s Republic of China"},{"name":"Guangdong Provincial Key Laboratory of Pharmaceutical Functional Genes, Ministry of Education Key Laboratory of Gene Function and Regulation, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1089-2252","authenticated-orcid":false,"given":"Yulan","family":"Weng","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Pharmaceutical Functional Genes, Ministry of Education Key Laboratory of Gene Function and Regulation, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9341-0030","authenticated-orcid":false,"given":"Lu","family":"Wang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Pharmaceutical Functional Genes, Ministry of Education Key Laboratory of Gene Function and Regulation, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7479-0180","authenticated-orcid":false,"given":"Xiaoli","family":"Fan","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Pharmaceutical Functional Genes, Ministry of Education Key Laboratory of Gene Function and Regulation, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai-Bo","family":"Zhao","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Pharmaceutical Functional Genes, Ministry of Education Key Laboratory of Gene Function and Regulation, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, People\u2019s Republic of 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai-Tian","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4405-1048","authenticated-orcid":false,"given":"Li","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou 510060, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8281-1450","authenticated-orcid":false,"given":"Limin","family":"Zheng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Guangdong 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Luo Cholinergic macrophages promote resolution of peritoneal inflammation. CNGBdb. Available at https:\/\/db.cngb.org\/search\/project\/CNP0005278. Deposited 24 May 2024."},{"key":"e_1_3_4_49_2","unstructured":"C. Wu Codes for \u201cCholinergic macrophages promote the resolution of peritoneal inflammation.\u201d GitHub. Available at https:\/\/github.com\/ChongEdwardWu\/PNAS_2024_ChEM. Deposited 13 June 2024."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2402143121","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T13:37:17Z","timestamp":1719409037000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2402143121"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,26]]},"references-count":49,"journal-issue":{"issue":"27","published-print":{"date-parts":[[2024,7,2]]}},"alternative-id":["10.1073\/pnas.2402143121"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2402143121","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,26]]},"assertion":[{"value":"2024-01-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-31","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2402143121"}}