Gut microbial metabolite targets HDAC3-FOXK1-interferon axis in fibroblast-like synoviocytes to ameliorate rheumatoid arthritis
作者机构：Department of Systems BiologySchool of Life SciencesSouthern University of Science and TechnologyGuangdong Provincial Key Laboratory of Cell Microenvironment and Disease ResearchShenzhen Key Laboratory of Cell MicroenvironmentShenzhen 518055China Institute of Integrated Bioinfomedicine and Translational Science(IBTS)School of Chinese MedicineHong Kong Baptist UniversityHong Kong SAR 999077China Department of BiochemistrySchool of MedicineSouthern University of Science and TechnologyGuangdong Provincial Key Laboratory of Cell Microenvironment and Disease ResearchShenzhen Key Laboratory of Cell MicroenvironmentShenzhen 518055China Division of Immunology and RheumatologyStanford UniversityStanfordCA 94305USA VA Palo Alto Health Care SystemPalo AltoCA 94304USA Institute of Plant and Food ScienceDepartment of BiologySouthern University of Science and TechnologyShenzhen 518055China Department of RheumatologyGuanghua Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai University of Traditional Chinese MedicineShanghaiChina Department of Computational BiologySt.Jude Children’s Research HospitalMemphisTNUSA Department of Laboratory MedicinePeking University Shenzhen HospitalShenzhenChina Guangdong-Hong Kong-Macao Joint Lab on Chinese Medicine and Immune Disease ResearchGuangzhou 510006China Shanghai University of Traditional Chinese MedicineShanghai 200032China State Key Laboratory of ProteomicsNational Center for Protein Sciences(Beijing)Beijing Institute of Lifeomics100850 BeijingChina
出 版 物：《Bone Research》 (骨研究（英文版）)
年 卷 期：2024年第12卷第2期
页 面：421-437页
核心收录：
学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学]
基 金：supported by the National Natural Science Foundation Council of China(82172386 and 81922081 to C.L.,82100943 to X.F.,82104216 to J.L.,and 82230081,82250710175 and 8226116039 to G.X.) the Department of Education of Guangdong Province(2021KTSCX104 to C.L.) the 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund(Guangdong-Hong Kong-Macao Joint Lab)(2020B1212030006 to A.L.) the Guangdong Provincial Science and Technology Innovation Council Grant(2017B030301018 to G.X.) the Guangdong Basic and Applied Basic Research Foundation(2022A1515012164 to C.L.,and 2023A1515012000 to X.F.) the Science,Technology and Innovation Commission of Shenzhen(JCYJ20210324104201005 to C.L.,JCYJ20220530115006014 to X.F.,JCYJ20230807095118035 to J.L.,and JCYJ20220818100617036 to G.X.) the Hong Kong General Research Fund(12102722 to A.L.) the Hong Kong RGC Themebased Research Scheme(T12-201/20-R to A.L.)
主 题：HDAC3 cytes interferon
摘 要：Rheumatoid arthritis(RA)is an autoimmune *** studies hold an opinion that gut microbiota is environmentally acquired and associated with RA ***,accumulating evidence demonstrates that genetics also shape the gut *** is known that some strains of inbred laboratory mice are highly susceptible to collagen-induced arthritis(CIA),while the others are resistant to ***,we show that transplantation of fecal microbiota of CIA-resistant C57BL/6J mice to CIA-susceptible DBA/1J mice confer CIA resistance in DBA/1J mice.C57BL/6J mice and healthy human individuals have enriched *** than DBA/1J mice and RA *** of *** prevents CIA in DBA/1J *** identify that *** mainly produces propionate and C57BL/6J mice and healthy human individuals have higher level of ***-like synoviocytes(FLSs)in RA are activated to undergo tumor-like *** disrupts HDAC3-FOXK1 interaction to increase acetylation of FOXK1,resulting in reduced FOXK1 stability,blocked interferon signaling and deactivation of *** treat CIA mice with propionate and show that propionate attenuates ***,a combination of propionate with anti-TNF etanercept synergistically relieves *** results suggest that *** or propionate could be an alternative or complementary approach to the current therapies.
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