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Article: TLR4+CXCR4+ plasma cells drive nephritis development in systemic lupus erythematosus

TitleTLR4+CXCR4+ plasma cells drive nephritis development in systemic lupus erythematosus
Authors
Keywordsautoimmune diseases
autoantibodies
systemic lupus erythematosus
lupus nephritis
B cells
Issue Date2018
Citation
Annals of the Rheumatic Diseases, 2018 How to Cite?
Abstract© Author(s) (or their employer(s)) 2018. No commercial re-use. See rights and permissions. Published by BMJ. Objectives: In patients with systemic lupus erythematosus (SLE), immune tolerance breakdown leads to autoantibody production and immune-complex glomerulonephritis. This study aimed to identify pathogenic plasma cells (PC) in the development of lupus nephritis. Methods: PC subsets in peripheral blood and renal tissue of patients with SLE and lupus mice were examined by flow cytometry and confocal microscopy, respectively. Sorting-purified PCs from lupus mice were adoptively transferred into Rag2-deficient recipients, in which immune-complex deposition and renal pathology were investigated. In culture, PCs from lupus mice and patients with SLE were treated with a TLR4 inhibitor and examined for autoantibody secretion by enzyme-linked immunospot assay (ELISPOT). Moreover, lupus mice were treated with a TLR4 inhibitor, followed by the assessment of serum autoantibody levels and glomerulonephritis activity. Results: The frequencies of TLR4+CXCR4+ PCs in peripheral blood and renal tissue were found significantly increased with the potent production of anti-dsDNA IgG, which were associated with severe renal damages in patients with SLE and mice with experimental lupus. Adoptive transfer of TLR4+CXCR4+ PCs from lupus mice led to autoantibody production and glomerulonephritis development in Rag2-deficient recipients. In culture, TLR4+CXCR4+ PCs from both lupus mice and patients with SLE showed markedly reduced anti-dsDNA IgG secretion on TLR4 blockade. Moreover, in vivo treatment with TLR4 inhibitor significantly attenuated autoantibody production and renal damages in lupus mice. Conclusions: These findings demonstrate a pathogenic role of TLR4+CXCR4+ PCs in the development of lupus nephritis and may provide new therapeutic strategies for the treatment of SLE.
Persistent Identifierhttp://hdl.handle.net/10722/279355
ISSN
2017 Impact Factor: 12.35
2015 SCImago Journal Rankings: 4.537
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorMa, Kongyang-
dc.contributor.authorLi, Jingyi-
dc.contributor.authorWang, Xiaohui-
dc.contributor.authorLin, Xiang-
dc.contributor.authorDu, Wenhan-
dc.contributor.authorYang, Xi-
dc.contributor.authorMou, Fangxiang-
dc.contributor.authorFang, Yongfei-
dc.contributor.authorZhao, Yanbin-
dc.contributor.authorHong, Xiaoping-
dc.contributor.authorChan, Kwok Wah-
dc.contributor.authorZhang, Xiaoming-
dc.contributor.authorLiu, Dongzhou-
dc.contributor.authorSun, Lingyun-
dc.contributor.authorLu, Liwei-
dc.date.accessioned2019-10-28T03:02:26Z-
dc.date.available2019-10-28T03:02:26Z-
dc.date.issued2018-
dc.identifier.citationAnnals of the Rheumatic Diseases, 2018-
dc.identifier.issn0003-4967-
dc.identifier.urihttp://hdl.handle.net/10722/279355-
dc.description.abstract© Author(s) (or their employer(s)) 2018. No commercial re-use. See rights and permissions. Published by BMJ. Objectives: In patients with systemic lupus erythematosus (SLE), immune tolerance breakdown leads to autoantibody production and immune-complex glomerulonephritis. This study aimed to identify pathogenic plasma cells (PC) in the development of lupus nephritis. Methods: PC subsets in peripheral blood and renal tissue of patients with SLE and lupus mice were examined by flow cytometry and confocal microscopy, respectively. Sorting-purified PCs from lupus mice were adoptively transferred into Rag2-deficient recipients, in which immune-complex deposition and renal pathology were investigated. In culture, PCs from lupus mice and patients with SLE were treated with a TLR4 inhibitor and examined for autoantibody secretion by enzyme-linked immunospot assay (ELISPOT). Moreover, lupus mice were treated with a TLR4 inhibitor, followed by the assessment of serum autoantibody levels and glomerulonephritis activity. Results: The frequencies of TLR4+CXCR4+ PCs in peripheral blood and renal tissue were found significantly increased with the potent production of anti-dsDNA IgG, which were associated with severe renal damages in patients with SLE and mice with experimental lupus. Adoptive transfer of TLR4+CXCR4+ PCs from lupus mice led to autoantibody production and glomerulonephritis development in Rag2-deficient recipients. In culture, TLR4+CXCR4+ PCs from both lupus mice and patients with SLE showed markedly reduced anti-dsDNA IgG secretion on TLR4 blockade. Moreover, in vivo treatment with TLR4 inhibitor significantly attenuated autoantibody production and renal damages in lupus mice. Conclusions: These findings demonstrate a pathogenic role of TLR4+CXCR4+ PCs in the development of lupus nephritis and may provide new therapeutic strategies for the treatment of SLE.-
dc.languageeng-
dc.relation.ispartofAnnals of the Rheumatic Diseases-
dc.subjectautoimmune diseases-
dc.subjectautoantibodies-
dc.subjectsystemic lupus erythematosus-
dc.subjectlupus nephritis-
dc.subjectB cells-
dc.titleTLR4+CXCR4+ plasma cells drive nephritis development in systemic lupus erythematosus-
dc.typeArticle-
dc.description.natureLink_to_subscribed_fulltext-
dc.identifier.doi10.1136/annrheumdis-2018-213615-
dc.identifier.pmid29925508-
dc.identifier.scopuseid_2-s2.0-85048885201-
dc.identifier.hkuros291529-
dc.identifier.spage1498-
dc.identifier.epage1506-
dc.identifier.eissn1468-2060-
dc.identifier.isiWOS:000446465700027-

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