Hspa13 Deficiency Impaired Marginal Zone B Cells Regulatory Function and Contributed to Lupus Pathogenesis
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...
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Wiley
2025-02-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202413144 |
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| author | Chen Xing Haoran Cui Ge Li Xiaoling Liu Kun Liu Qing Wen Xin Huang Renxi Wang Lun Song |
| author_facet | Chen Xing Haoran Cui Ge Li Xiaoling Liu Kun Liu Qing Wen Xin Huang Renxi Wang Lun Song |
| author_sort | Chen Xing |
| collection | DOAJ |
| description | 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 CD19creHspa13fl/fl mice for Breg induction show an impaired capacity to promote CD4+Foxp3+ 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 CD19creHspa13fl/fl 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. |
| format | Article |
| id | doaj-art-31ea677333004db2b6ed62a68d25dac4 |
| institution | DOAJ |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
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| series | Advanced Science |
| spelling | doaj-art-31ea677333004db2b6ed62a68d25dac42025-08-20T03:09:54ZengWileyAdvanced Science2198-38442025-02-01128n/an/a10.1002/advs.202413144Hspa13 Deficiency Impaired Marginal Zone B Cells Regulatory Function and Contributed to Lupus PathogenesisChen Xing0Haoran Cui1Ge Li2Xiaoling Liu3Kun Liu4Qing Wen5Xin Huang6Renxi Wang7Lun Song8Beijing Institute of Basic Medical Sciences Beijing 100850 ChinaBeijing Institute of Basic Medical Sciences Beijing 100850 ChinaBeijing Institute of Basic Medical Sciences Beijing 100850 ChinaDepartment of Dermatology First Medical Centre of Chinese PLA General Hospital Beijing 100853 ChinaBeijing Institute of Basic Medical Sciences Beijing 100850 ChinaBeijing Institute of Basic Medical Sciences Beijing 100850 ChinaBeijing Institute of Basic Medical Sciences Beijing 100850 ChinaBeijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology Collaborative Innovation Center for Brain Disorders Capital Medical University Beijing 100069 ChinaBeijing Institute of Basic Medical Sciences Beijing 100850 ChinaAbstract 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 CD19creHspa13fl/fl mice for Breg induction show an impaired capacity to promote CD4+Foxp3+ 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 CD19creHspa13fl/fl 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.https://doi.org/10.1002/advs.202413144Hspa13IL‐10MZ B cellsregulatory B cellsregulatory T cellsSLE |
| spellingShingle | Chen Xing Haoran Cui Ge Li Xiaoling Liu Kun Liu Qing Wen Xin Huang Renxi Wang Lun Song Hspa13 Deficiency Impaired Marginal Zone B Cells Regulatory Function and Contributed to Lupus Pathogenesis Advanced Science Hspa13 IL‐10 MZ B cells regulatory B cells regulatory T cells SLE |
| title | Hspa13 Deficiency Impaired Marginal Zone B Cells Regulatory Function and Contributed to Lupus Pathogenesis |
| title_full | Hspa13 Deficiency Impaired Marginal Zone B Cells Regulatory Function and Contributed to Lupus Pathogenesis |
| title_fullStr | Hspa13 Deficiency Impaired Marginal Zone B Cells Regulatory Function and Contributed to Lupus Pathogenesis |
| title_full_unstemmed | Hspa13 Deficiency Impaired Marginal Zone B Cells Regulatory Function and Contributed to Lupus Pathogenesis |
| title_short | Hspa13 Deficiency Impaired Marginal Zone B Cells Regulatory Function and Contributed to Lupus Pathogenesis |
| title_sort | hspa13 deficiency impaired marginal zone b cells regulatory function and contributed to lupus pathogenesis |
| topic | Hspa13 IL‐10 MZ B cells regulatory B cells regulatory T cells SLE |
| url | https://doi.org/10.1002/advs.202413144 |
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