Potential role of interleukin-33 in systemic lupus erythematosus by regulating toll like receptor 4

• Published in: European journal of inflammation 2022-04, Vol.20
• Main Authors: Li, Yi, Shao, Yijia, He, Yan, Li, Qiugen, Duan, Lihua
• Format: Article
• Language: English
• Subjects: Autoimmune diseases; Cytokines; Inflammation; Lupus; Pathogenesis; Protein expression
• ISSN: 1721-727X; 2058-7392
• DOI: 10.1177/1721727X221094455

Introduction Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by immune activation and multi-immunologic phenotypes. Interleukin-33 (IL-33) has been shown to be a critical and pleiotropic immunoregulatory mediator in the pathogenesis of many autoimmune diseases. At present, there are conflicting findings in the research of IL-33 in SLE. The purpose of this study was to investigate whether and how IL-33 is involved in the occurrence and development of SLE. Methods 43 SLE patients and 43 healthy volunteers were recruited for this study. Serum levels of IL-33, IL-4, IL-6, IL-10 and IL-21 were measured by ELISA. The expression of IL-33 was investigated in kidney sections by immunohistochemistry in lupus nephritis patients (n = 5) and controls (n = 3). The mRNA expressions of Toll like receptor 4 (TLR4), TLR2, and tumorigenicity 2 (ST2)L were quantified in peripheral blood mononuclear cells (PBMCs) by real-time PCR. The surface expression of TLR4 on T cells, B cells, monocytes, and neutrophils was assessed by flow cytometry (n = 22). Mann–Whitney U-test and Spearman’s test were used for statistical analysis. Results Serum concentrations of IL-33 were significantly higher in SLE patients than in healthy controls (p < 0.0001). IL-33 expressions were positively correlated with IL-4 and IL-6 levels in SLE patients, which play pivotal roles in the autoantibody production. In addition, TLR4 and TLR2 mRNA were markedly increased in PBMCs from SLE patients (p < 0.05). TLR4 was positively associated with IL-33, while TLR2 was not. Conclusions These results imply that upregulated expression of serum IL-33 together with increased TLR4 in PBMCs may contribute to the pathogenesis of SLE via promotion of inflammatory cytokines production.