| Autor: |
Lingxiao, Xu, Lei, Wang, Yumeng, Shi, Yun, Deng, Jim C, Oates, Diane L, Kamen, Gary S, Gilkeson, Fang, Wang, Miaojia, Zhang, Wenfeng, Tan, Betty P, Tsao |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
Arthritisrheumatology (Hoboken, N.J.)REFERENCES. 74(3) |
| ISSN: |
2326-5205 |
| Popis: |
Elevated interleukin-10 (IL-10) levels in patients with systemic lupus erythematosus (SLE) have B cell-promoting effects, contributing to autoantibody production and tissue damage. We aimed to characterize up-regulated IL-10+ B cell subsets and dysregulated IL10 expression in SLE B cells for new therapeutic options.Proportions of Th10 and IL-10+ B cell subsets in peripheral blood mononuclear cells (PBMCs) were assessed using flow cytometry. The IL10 3'-untranslated region (3'-UTR) dual-luciferase vector was constructed and cotransfected with small interfering RNA (siRNA), microRNA (miRNA) mimics, or miRNA inhibitors into Raji cells. Transcript levels were quantified using TaqMan assays.Culture conditions that induced IL-10+ Breg cells in healthy controls resulted in expansion of IL-10+ double-negative 2 (DN2; IgD-CD27-CD21-CD11c+) B cells in SLE PBMCs. Proportions of IL-10+ DN2, but not those of IL-10- DN2, correlated with disease activity and levels of antibodies to double-stranded DNA (dsDNA) (r = 0.60, P = 0.03 for cohort 1; r = 0.38, P = 0.03 for cohort 2), and were associated with high levels or seropositivity of anti-Sm (P = 0.03 for cohort 1; P = 0.01 for cohort 2) and IgG anticardiolipin (P 0.01 for cohort 1; P = 0.02 for cohort 2) in SLE patients from 2 cohorts, of mainly African American subjects (cohort 1) and of Asian subjects (cohort 2). Proportions of Th10 (CD45RA-CXCR5-CXCR3+PD-1IL-10 promotes extrafollicular autoimmune responses in patients with active SLE, which might be dampened by targeting the E2F2-miR-17-5p circuitry. |
| Databáze: |
OpenAIRE |
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