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NLRP3 protein expression is considered as the rate-limiting step for NLRP3 inflammasome activation. In this study, we show that galectin-9 (encoded by lgals9) attenuated NLRP3 inflammasome activation by promoting the protein degradation of NLRP3 in primary peritoneal macrophages of C57BL\/6J mice. Lgals9 deficiency enhances NLRP3 inflammasome activation and promotes NLRP3-dependent inflammation in C57BL\/6J mice in vivo. Mechanistically, galectin-9 interacts with NLRP3, promotes the formation of NLRP3\/p62 (an autophagic cargo receptor, also known as SQSTM1) complex, and thus facilitates p62-dependent autophagic degradation of NLRP3 in primary peritoneal macrophages of C57BL\/6J mice and HEK293T cells. Therefore, we identify galectin-9 as an \u201ceat-me\u201d signal for selective autophagy of NLRP3 and uncover the potential roles of galectins in controlling host protein degradation. Furthermore, our work suggests galectin-9 as a priming therapeutic target for the diseases caused by improper NLRP3 inflammasome activation.<\/jats:p>","DOI":"10.4049\/jimmunol.2001404","type":"journal-article","created":{"date-parts":[[2021,5,7]],"date-time":"2021-05-07T14:16:20Z","timestamp":1620396980000},"page":"2692-2699","source":"Crossref","is-referenced-by-count":33,"title":["Galectin-9 Targets NLRP3 for Autophagic Degradation to Limit Inflammation"],"prefix":"10.1093","volume":"206","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1162-4797","authenticated-orcid":false,"given":"Wenwen","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Immunology, Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University , Jinan, Shandong ,","place":["China"]},{"name":"State Key Laboratory of Microbial Technology, Shandong University , Jinan, Shandong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Immunology, Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University , Jinan, Shandong ,","place":["China"]},{"name":"State Key Laboratory of Microbial Technology, Shandong University , Jinan, Shandong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Immunology, Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University , Jinan, Shandong ,","place":["China"]},{"name":"State Key Laboratory of Microbial Technology, Shandong University , Jinan, Shandong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Pathology Tissue Bank, Qilu Hospital, Cheeloo College of Medicine, Shandong University , Jinan, Shandong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2652-3411","authenticated-orcid":false,"given":"Mutian","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Immunology, Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University , Jinan, Shandong ,","place":["China"]},{"name":"State Key Laboratory of Microbial Technology, Shandong University , Jinan, Shandong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyuan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Immunology, Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University , Jinan, Shandong ,","place":["China"]},{"name":"State Key Laboratory of Microbial Technology, Shandong University , Jinan, Shandong ,","place":["China"]},{"name":"Department of Cell Biology, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University , Jinan, Shandong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6233-4706","authenticated-orcid":false,"given":"Mouchun","family":"Gong","sequence":"additional","affiliation":[{"name":"Hangzhou Medical College Affiliated Lin\u2019an People\u2019s Hospital , Hangzhou, Zhejiang ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8440-2274","authenticated-orcid":false,"given":"Wei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Immunology, Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University , Jinan, Shandong ,","place":["China"]},{"name":"State Key Laboratory of Microbial Technology, Shandong University , Jinan, Shandong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,6,1]]},"reference":[{"key":"2025030417503679700_r1","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/s41577-019-0165-0","article-title":"The NLRP3 inflammasome: molecular activation and regulation to therapeutics","volume":"19","author":"Swanson","year":"2019","journal-title":"Nat. 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