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

Autor: 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.; Department of Microbiology, Ewha Womans University, Seoul, Republic of Korea., Jenks SA; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, School of Medicine, Emory University, Atlanta, GA, USA., 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 Pulmonary, Allergy, Critical Care and Sleep Medicine, School of Medicine, Emory University, Atlanta, GA, USA., Wei C; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, School of Medicine, Emory University, Atlanta, GA, USA., Scharer CD; Department of Microbiology and 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 Medicine, Division of Rheumatology, Lowance Center for Human Immunology, School of Medicine, Emory University, Atlanta, GA, USA., Nguyen DC; Department of Medicine, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, School of Medicine, Emory University, Atlanta, GA, USA., Khosroshahi A; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, 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 Pulmonary, Allergy, Critical Care and Sleep Medicine, School of Medicine, Emory University, Atlanta, GA, USA. f.e.lee@emory.edu., Sanz I; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, School of Medicine, Emory University, Atlanta, GA, USA. ignacio.sanz@emory.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Mar 01; Vol. 15 (1), pp. 1899. Date of Electronic Publication: 2024 Mar 01.
DOI: 10.1038/s41467-024-46053-w
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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