IFN-α affects Th17/Treg cell balance through c-Maf and associated with the progression of EBV- SLE.

Autor: Zhang Y; Department of Immunology, Hebei Medical University, Shijiazhuang, Hebei, China; Key Laboratory of Immune mechanism and Intervention on Serious Disease in Hebei Province, Shijiazhuang, Hebei, China; Department of Rheumatology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China., Wang J; Department of Immunology, Hebei Medical University, Shijiazhuang, Hebei, China; Key Laboratory of Immune mechanism and Intervention on Serious Disease in Hebei Province, Shijiazhuang, Hebei, China., Fang Y; Department of Immunology, Hebei Medical University, Shijiazhuang, Hebei, China; Key Laboratory of Immune mechanism and Intervention on Serious Disease in Hebei Province, Shijiazhuang, Hebei, China., Liang W; Department of Immunology, Hebei Medical University, Shijiazhuang, Hebei, China; Key Laboratory of Immune mechanism and Intervention on Serious Disease in Hebei Province, Shijiazhuang, Hebei, China., Lei L; Department of Rheumatology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China., Wang J; Department of Immunology, Hebei Medical University, Shijiazhuang, Hebei, China; Key Laboratory of Immune mechanism and Intervention on Serious Disease in Hebei Province, Shijiazhuang, Hebei, China., Gao X; Department of Immunology, Hebei Medical University, Shijiazhuang, Hebei, China; Key Laboratory of Immune mechanism and Intervention on Serious Disease in Hebei Province, Shijiazhuang, Hebei, China., Ma C; Department of Immunology, Hebei Medical University, Shijiazhuang, Hebei, China; Key Laboratory of Immune mechanism and Intervention on Serious Disease in Hebei Province, Shijiazhuang, Hebei, China., Li M; Department of Immunology, Hebei Medical University, Shijiazhuang, Hebei, China; Key Laboratory of Immune mechanism and Intervention on Serious Disease in Hebei Province, Shijiazhuang, Hebei, China., Guo H; Department of Rheumatology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China. Electronic address: guohfch@126.com., Wei L; Department of Immunology, Hebei Medical University, Shijiazhuang, Hebei, China; Key Laboratory of Immune mechanism and Intervention on Serious Disease in Hebei Province, Shijiazhuang, Hebei, China. Electronic address: weilin@hebmu.edu.cn.
Jazyk: angličtina
Zdroj: Molecular immunology [Mol Immunol] 2024 Jul; Vol. 171, pp. 22-35. Date of Electronic Publication: 2024 May 14.
DOI: 10.1016/j.molimm.2024.05.003
Abstrakt: Objectives: Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease, of which the pathogens is remains obscure. Viral infection, particularly Epstein Barr viru (EBV) infection, has been considered a common pathogenic factor. This study suggests that c-Maf may be an important target in T cell differentiation during SLE progression, providing a potentially new perspective on the role of viral infection in the pathogenesis of autoimmune diseases.
Methods: Cytokines of EBV-infected SLE patients were measured by ELISA and assessed in conjunction with their clinical data. IFN-α, c-Maf, and the differentiation of Th17/Treg cells in SLE patients and MRL/LPR mice were analyzed using FCM, WB, RT-PCR, etc. Following the infection of cells and mice with EBV or viral mimic poly (dA:dT), the changes of the aforementioned indicators were investigated. The relationship among IFN-α, STAT3, c-Maf and Th17 cells was determined by si-RNA technique.
Results: Many SLE patients are found to be complicated by viral infections; Further, studies have demonstrated that viral infection, especially EBV, is involved in SLE development. This study showed that viral infections might promote IFN-α secretion, inhibit c-Maf expression by activating STAT3, increase Th17 cell differentiation, and lead to the immune imbalance of Th17/Treg cells, thus playing a role in the onset and progression of SLE.
Conclusion: This study demonstrates that EBV infections may contribute to SLE development by activating STAT3 through IFN-α, inhibiting c-Maf, and causing Th17/Treg immune imbalance. Our work provided a new insight into the pathogenesis and treatment of SLE.
Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest.
(Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE