Elevated IL-15 levels in systemic lupus erythematosus: potential pathogenesis insight and therapeutic target.

Autor: Jiang J; Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, Jiangsu, China; Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China; Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing, Jiangsu, China; Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing, Jiangsu, China., Yang M; Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China., Yang B; Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China., Wu H; Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China. Electronic address: chriswu1010@126.com., Lu Q; Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, Jiangsu, China; Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China; Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing, Jiangsu, China; Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing, Jiangsu, China. Electronic address: qianlu5860@pumcderm.cams.cn.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2024 Dec 05; Vol. 142 (Pt A), pp. 112973. Date of Electronic Publication: 2024 Aug 31.
DOI: 10.1016/j.intimp.2024.112973
Abstrakt: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by persistent immune cell activation and the overproduction of autoantibodies, affecting various organs such as joints, kidneys, and skin. Interleukin-15 (IL-15) is a pleiotropic cytokine that modulates immune cells of the innate and adaptive immune systems, playing a crucial role in the development of inflammatory and protective immune responses. However, the role of IL-15 in SLE pathogenesis and the therapeutic effects of IL-15 blockade on SLE remain unknown. In this study, we conducted flow cytometry analysis and identified a significant increase in the frequencies of IL-15 + and IL-15R + cells in peripheral blood CD4 + T cells, CD8 + T cells, dendritic cells (DCs), monocytes, and natural killer (NK) cells of patients with SLE compared to healthy controls (HCs). Besides, we found elevated levels of serum IL-15 in SLE patients compared to HCs. Furthermore, we evaluted the effectiveness of IL-15 mAb treatment in a chronic graft-versus-host disease (cGVHD) mouse model of SLE. We observed that the IL-15 mAb treatment effectively reduced the frequencies of CD4 + CD44 hi CD62L lo PD-1 + CD153 + senescent CD4 + T cells, B220 + CD11c + T-bet + age-associated B cells (ABCs), Tfh cells, and germinal center (GC) B cells, alleviated lupus-associated manifestations such as serum anti-double-stranded DNA antibody (anti-dsDNA) and kidney injury in the SLE mouse model of cGVHD. These findings provide compelling preclinical evidence suggesting the pathogenic role of IL-15 in SLE and the therapeutic potential of IL-15 blockade in the treatment of SLE.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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