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Distinct transcriptomes and autocrine cytokines underpin maturation and survival of antibody-secreting cells in systemic lupus erythematosus.
Chen, Weirong; Hong, So-Hee; Jenks, Scott A; Anam, Fabliha A; Tipton, Christopher M; Woodruff, Matthew C; Hom, Jennifer R; Cashman, Kevin S; Faliti, Caterina Elisa; Wang, Xiaoqian; Kyu, Shuya; Wei, Chungwen; Scharer, Christopher D; Mi, Tian; Hicks, Sakeenah; Hartson, Louise; Nguyen, Doan C; Khosroshahi, Arezou; Lee, Saeyun; Wang, Youliang; Bugrovsky, Regina; Ishii, Yusho; Lee, F Eun-Hyung; Sanz, Ignacio.
Affiliation
  • Chen W; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, School of Medicine, Emory University, Atlanta, GA, USA.
  • Hong SH; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, School of Medicine, Emory University, Atlanta, GA, USA.
  • Jenks SA; Department of Microbiology, Ewha Womans University, Seoul, Republic of Korea.
  • Anam FA; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, School of Medicine, Emory University, Atlanta, GA, USA.
  • Tipton CM; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, School of Medicine, Emory University, Atlanta, GA, USA.
  • Woodruff MC; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, School of Medicine, Emory University, Atlanta, GA, USA.
  • Hom JR; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, School of Medicine, Emory University, Atlanta, GA, USA.
  • Cashman KS; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, School of Medicine, Emory University, Atlanta, GA, USA.
  • Faliti CE; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, School of Medicine, Emory University, Atlanta, GA, USA.
  • Wang X; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, School of Medicine, Emory University, Atlanta, GA, USA.
  • Kyu S; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, School of Medicine, Emory University, Atlanta, GA, USA.
  • Wei C; Department of Medicine, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, School of Medicine, Emory University, Atlanta, GA, USA.
  • Scharer CD; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, School of Medicine, Emory University, Atlanta, GA, USA.
  • Mi T; Department of Microbiology and Immunology, School of Medicine, Emory University, Atlanta, GA, USA.
  • Hicks S; Department of Microbiology and Immunology, School of Medicine, Emory University, Atlanta, GA, USA.
  • Hartson L; Department of Microbiology and Immunology, School of Medicine, Emory University, Atlanta, GA, USA.
  • Nguyen DC; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, School of Medicine, Emory University, Atlanta, GA, USA.
  • Khosroshahi A; Department of Medicine, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, School of Medicine, Emory University, Atlanta, GA, USA.
  • Lee S; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, School of Medicine, Emory University, Atlanta, GA, USA.
  • Wang Y; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, School of Medicine, Emory University, Atlanta, GA, USA.
  • Bugrovsky R; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, School of Medicine, Emory University, Atlanta, GA, USA.
  • Ishii Y; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, School of Medicine, Emory University, Atlanta, GA, USA.
  • Lee FE; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, School of Medicine, Emory University, Atlanta, GA, USA.
  • Sanz I; Department of Medicine, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, School of Medicine, Emory University, Atlanta, GA, USA. f.e.lee@emory.edu.
Nat Commun ; 15(1): 1899, 2024 Mar 01.
Article in En | MEDLINE | ID: mdl-38429276
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Autoimmune Diseases / Lupus Erythematosus, Systemic Limits: Humans Language: En Journal: Nat Commun Year: 2024 Document type: Article
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Autoimmune Diseases / Lupus Erythematosus, Systemic Limits: Humans Language: En Journal: Nat Commun Year: 2024 Document type: Article