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An immunomodulatory role of heat shock proteins (HSPs) is implicated in autoimmune diseases. However, the molecular basis underlying the role of Hspa13 in regulating Bregs function and lupus pathogenesis remains unclear. In this study, Bregs display higher Hspa13 expression than IL\u201010<jats:sup>\u2212<\/jats:sup> B cells. Induction of IL\u201010 production is weakened in B cells with Hspa13 knockdown or knockout. Hspa13 binds to the IL\u201010 promoter via the TATA or CAAT box and activates IL\u201010 transcription in the nucleus. Furthermore, Hspa13 positive cells are enriched in marginal zone (MZ) B cells to regulate IL\u201010 production. Stimulated B220<jats:sup>+<\/jats:sup> B or MZ B cells from CD19<jats:sup>cre<\/jats:sup>Hspa13<jats:sup>fl\/fl<\/jats:sup> mice for Breg induction show an impaired capacity to promote CD4<jats:sup>+<\/jats:sup>Foxp3<jats:sup>+<\/jats:sup> regulatory T cells (Treg) differentiation. In lupus MRL\/lpr mice, a decline in Treg differentiation is accompanied by decreased Hspa13 expression in both Bregs and MZ B cells. Moreover, adoptive transfusion of Bregs and MZ B cells from CD19<jats:sup>cre<\/jats:sup>Hspa13<jats:sup>fl\/fl<\/jats:sup> mice fails to increase the frequency of Tregs, attenuate renal pathology, or decrease anti\u2010dsDNA antibody levels. These results explain the unique role of Hspa13 in determining MZ regulatory function and affecting lupus pathogenesis.<\/jats:p>","DOI":"10.1002\/advs.202413144","type":"journal-article","created":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T07:17:17Z","timestamp":1735629437000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Hspa13 Deficiency Impaired Marginal Zone B Cells Regulatory Function and Contributed to Lupus Pathogenesis"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2784-840X","authenticated-orcid":false,"given":"Chen","family":"Xing","sequence":"first","affiliation":[{"name":"Beijing Institute of Basic Medical Sciences  Beijing 100850 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoran","family":"Cui","sequence":"additional","affiliation":[{"name":"Beijing Institute of Basic Medical Sciences  Beijing 100850 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ge","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing Institute of Basic Medical Sciences  Beijing 100850 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoling","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Dermatology First Medical Centre of Chinese PLA General Hospital  Beijing 100853 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Liu","sequence":"additional","affiliation":[{"name":"Beijing Institute of Basic Medical Sciences  Beijing 100850 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Wen","sequence":"additional","affiliation":[{"name":"Beijing Institute of Basic Medical Sciences  Beijing 100850 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Huang","sequence":"additional","affiliation":[{"name":"Beijing Institute of Basic Medical Sciences  Beijing 100850 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renxi","family":"Wang","sequence":"additional","affiliation":[{"name":"Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology Collaborative Innovation Center for Brain Disorders Capital Medical University  Beijing 100069 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lun","family":"Song","sequence":"additional","affiliation":[{"name":"Beijing Institute of Basic Medical Sciences  Beijing 100850 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,31]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2018.11.001"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20236021"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.611795"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.14763"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-005-0355-6"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201546248"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.12.7868"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI46274"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.10.016"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2018.09.012"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2014.56"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-07-294249"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.11.009"},{"key":"e_1_2_9_14_1","first-page":"283","volume":"16","author":"Park Y. 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