Extracorporeal photopheresis reduces inflammation and joint damage in a rheumatoid arthritis murine model

• Published in: Journal of translational medicine 2024-03, Vol.22 (1), p.305-13, Article 305
• Main Authors: Lin, Yuwei, Cheng, Zhanrui, Zhong, Yan, Zhao, Yinting, Xiang, Guifen, Li, Ling, Tian, Li, Liu, Zhong
• Format: Article
• Language: English
• Subjects: Analysis; Animal models; Animals; Ankle; Antirheumatic agents; Arthritis, Experimental - therapy; Arthritis, Rheumatoid - drug therapy; Autoimmune diseases; Body weight; Care and treatment; Cartilage; Cattle; CD11b antigen; CD11c antigen; CD25 antigen; CD3 antigen; CD4 antigen; CD80 antigen; CD86 antigen; Cellular therapy; Collagen; Collagen Type II; Collagen-induced arthritis; Computed tomography; Cytokines; Cytokines - metabolism; Dendritic cells; Diagnosis; Disease Models, Animal; Dosage and administration; Drugs; Extracorporeal photopheresis; Fingers & toes; Flow cytometry; Foxp3 protein; Graft versus host disease; Helper cells; Hyperplasia; Immunoglobulin G; Immunological tolerance; Inflammation; Interleukin 6; Interleukin-17 - metabolism; Joint diseases; Lymphocytes T; Major histocompatibility complex; Mice; Mice, Inbred DBA; Patients; Photopheresis; Rheumatoid arthritis; T-Lymphocytes, Regulatory; Th17 Cells
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-024-05105-x

Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammatory reactions and tissue damage in the joints. Long-term drug use in clinical practice is often accompanied by adverse reactions. Extracorporeal photopheresis (ECP) is an immunomodulatory therapy with few side effects, offering a potential and safe therapeutic alternative for RA through the induction of immune tolerance. This study aimed to investigate the therapeutic effects of ECP on RA using a collagen-induced arthritis (CIA) murine model, as well as to explore its immunomodulatory effects in vivo. Additionally, particular attention was given to the significant role of monocytes during the ECP process. A murine model of rheumatoid arthritis was established by administering two injections of bovine type II collagen to DBA/1J mice. ECP, ECP-MD (mononuclear cells were depleted during the ECP), MTX, and PBS treatment were applied to the CIA mice. During the treatment process, clinical scores and body weight changes of CIA mice were closely monitored. After six treatment sessions, micro-CT images of the hind paws from live mice were captured. Ankle joints and paws of the mice were collected and processed for histological evaluation. Spleen samples were collected to measure the Th17/Treg cells ratio, and serum samples were collected to assess cytokine and anti-type II collagen IgG levels. Monocytes and dendritic cells populations before and after ECP in vitro were detected by flow cytometry. ECP therapy significantly attenuated the progression of CIA, alleviated the severity of clinical symptoms in CIA mice and effectively suppressed synovial hyperplasia, inflammation, and cartilage damage. There was an expansion in the percentage of CD3 + CD4 + CD25 + FoxP3 + Tregs and a decrease in CD3 + CD4 + IL17A + Th17 cells in vivo. Furthermore, ECP reduced the serum levels of pro-inflammatory cytokines IL-6 (53.47 ± 7.074 pg/mL vs 5.142 ± 1.779 pg/mL, P