Trichinella spiralis Paramyosin Alleviates Collagen-Induced Arthritis in Mice by Modulating CD4 + T Cell Differentiation

• Published in: International journal of molecular sciences 2024-06, Vol.25 (12), p.6706
• Main Authors: Zhang, Dongwan, Jiang, Wang, Yu, Yan, Huang, Jingjing, Jia, Zhihui, Cheng, Yuli, Zhu, Xinping
• Format: Article
• Language: English
• Subjects: Animals; Antigens; Arthritis; Arthritis, Experimental - drug therapy; Arthritis, Experimental - immunology; Arthritis, Experimental - pathology; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - immunology; Autoimmune diseases; B cells; Cartilage; CD4+ T cells; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Cell differentiation; Cell Differentiation - drug effects; Collagen; collagen-induced arthritis; Cytokines; Disease Models, Animal; Helminth Proteins - immunology; Helminth Proteins - pharmacology; Helminth Proteins - therapeutic use; hygiene hypothesis; Inflammatory bowel disease; Lymphocytes; Male; Mice; Mice, Inbred DBA; Proteins; Rheumatoid factor; T cell differentiation; T cells; T-Lymphocytes, Regulatory - immunology; Th1 Cells - immunology; Th17 Cells - immunology; Th17 Cells - metabolism; Trichinella spiralis - immunology; Trichinella spiralis paramyosin; Tropomyosin - immunology; Tumor necrosis factor-TNF
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25126706

Rheumatoid arthritis (RA) is an autoimmune disease that significantly impacts quality of life by disrupting CD4 T cell immune homeostasis. The identification of a low-side-effect drug for RA treatment is urgently needed. Our previous study suggests that paramyosin ( -Pmy) has immunomodulatory effects, but its potential effect on CD4 T cell response in RA remains unclear. In this study, we used a murine model to investigate the role of r -Pmy in regulating CD4 T cell differentiation in collagen-induced arthritis (CIA). Additionally, we assessed the impact of r -Pmy on CD4 T cell differentiation towards the Th1 and Th17 phenotypes, which are associated with inflammatory responses in arthritis, using in vitro assays. The results demonstrated that r -Pmy administration reduced arthritis severity by inhibiting Th1 and Th17 response while enhancing Treg response. Prophylactic administration of -Pmy showed superior efficacy on CIA compared to therapeutic administration. Furthermore, in vitro assays demonstrated that r -Pmy could inhibit the differentiation of CD4 T cells into Th1 and Th17 while inducing the production of Tregs, suggesting a potential mechanism underlying its therapeutic effects. This study suggests that -Pmy may ameliorate CIA by restoring the immune balance of CD4 T cells and provides new insights into the mechanism through which helminth-derived proteins exert their effects on autoimmune diseases.