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热休克蛋白家族A成员13（Hspa13）缺陷损害边缘区B细胞调节功能并促进狼疮发病机制。

Hspa13 Deficiency Impaired Marginal Zone B Cells Regulatory Function and Contributed to Lupus Pathogenesis.

作者信息

Xing Chen, Cui Haoran, Li Ge, Liu Xiaoling, Liu Kun, Wen Qing, Huang Xin, Wang Renxi, Song Lun

机构信息

Beijing Institute of Basic Medical Sciences, Beijing, 100850, China.

Department of Dermatology, First Medical Centre of Chinese, PLA General Hospital, Beijing, 100853, China.

出版信息

Adv Sci (Weinh). 2025 Feb;12(8):e2413144. doi: 10.1002/advs.202413144. Epub 2024 Dec 31.

DOI:10.1002/advs.202413144
PMID:39737854
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11848637/
Abstract

Dysregulated IL-10 producing regulatory B cells (Bregs) are associated with the progression of systemic lupus erythematosus. 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-10 B cells. Induction of IL-10 production is weakened in B cells with Hspa13 knockdown or knockout. Hspa13 binds to the IL-10 promoter via the TATA or CAAT box and activates IL-10 transcription in the nucleus. Furthermore, Hspa13 positive cells are enriched in marginal zone (MZ) B cells to regulate IL-10 production. Stimulated B220 B or MZ B cells from CD19Hspa13 mice for Breg induction show an impaired capacity to promote CD4Foxp3 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 CD19Hspa13 mice fails to increase the frequency of Tregs, attenuate renal pathology, or decrease anti-dsDNA antibody levels. These results explain the unique role of Hspa13 in determining MZ regulatory function and affecting lupus pathogenesis.

摘要

产生白细胞介素-10（IL-10）的调节性B细胞（Bregs）失调与系统性红斑狼疮的进展相关。热休克蛋白（HSPs）的免疫调节作用与自身免疫性疾病有关。然而，热休克蛋白A13（Hspa13）在调节Bregs功能和狼疮发病机制中作用的分子基础仍不清楚。在本研究中，Bregs比IL-10 B细胞表现出更高的Hspa13表达。在Hspa13敲低或敲除的B细胞中，IL-10产生的诱导减弱。Hspa13通过TATA或CAAT盒与IL-10启动子结合，并在细胞核中激活IL-10转录。此外，Hspa13阳性细胞在边缘区（MZ）B细胞中富集以调节IL-10产生。来自CD19Hspa13小鼠的经刺激的B220 B或MZ B细胞用于诱导Bregs时，促进CD4Foxp3调节性T细胞（Treg）分化的能力受损。在狼疮MRL/lpr小鼠中，Treg分化的下降伴随着Bregs和MZ B细胞中Hspa13表达的降低。此外，输注来自CD19Hspa13小鼠的Bregs和MZ B细胞不能增加Tregs的频率、减轻肾脏病理或降低抗双链DNA抗体水平。这些结果解释了Hspa13在决定MZ调节功能和影响狼疮发病机制中的独特作用。

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HSPA13 modulates type I interferon antiviral pathway and NLRP3 inflammasome to restrict dengue virus infection in macrophages.
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Heat shock protein Hspa13 regulates endoplasmic reticulum and cytosolic proteostasis through modulation of protein translocation.热休克蛋白 Hspa13 通过调节蛋白易位来调节内质网和细胞质的蛋白质稳态。
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