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Distinct transcriptomes and autocrine cytokines underpin maturation and survival of antibody-secreting cells in systemic lupus erythematosus

Title
Distinct transcriptomes and autocrine cytokines underpin maturation and survival of antibody-secreting cells in systemic lupus erythematosus
Authors
SakeenahHartsonLouiseNguyenDoan C.KhosroshahiArezouLeeSaeyunYouliangBugrovskyReginaIshiiYushoF. Eun-HyungSanzIgnacioChenWeirongHongSo-HeeJenksScott A.AnamFabliha A.TiptonChristopher M.WoodruffMatthew C.HomJennifer R.CashmanKevin S.FalitiCaterina ElisaWangXiaoqianKyuShuyaWeiChungwenScharerChristopher D.MiTianHicks
Ewha Authors
홍소희
SCOPUS Author ID
홍소희scopus
Issue Date
2024
Journal Title
Nature Communications
ISSN
2041-1723JCR Link
Citation
Nature Communications vol. 15, no. 1
Publisher
Nature Research
Indexed
SCIE; SCOPUS scopus
Document Type
Article
Abstract
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple autoantibody types, some of which are produced by long-lived plasma cells (LLPC). Active SLE generates increased circulating antibody-secreting cells (ASC). Here, we examine the phenotypic, molecular, structural, and functional features of ASC in SLE. Relative to post-vaccination ASC in healthy controls, circulating blood ASC from patients with active SLE are enriched with newly generated mature CD19−CD138+ ASC, similar to bone marrow LLPC. ASC from patients with SLE displayed morphological features of premature maturation and a transcriptome epigenetically initiated in SLE B cells. ASC from patients with SLE exhibited elevated protein levels of CXCR4, CXCR3 and CD138, along with molecular programs that promote survival. Furthermore, they demonstrate autocrine production of APRIL and IL-10, which contributed to their prolonged in vitro survival. Our work provides insight into the mechanisms of generation, expansion, maturation and survival of SLE ASC. © The Author(s) 2024.
DOI
10.1038/s41467-024-46053-w
Appears in Collections:
의과대학 > 의학과 > Journal papers
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