Abstract
Background Researches have confirmed that the abnormal signals of OX40 and PD-1 lead to the changes of T cell biological behavior, thus participating the immunopathological process of RA. However, the pathogenesis of RA immunopathological process has not been clarified yet. Methods 30 DBA/1 mice were randomly divided into 5 groups (6 mice per group): control group, collagen-induced arthritis (CIA) group, PD-1-Fc/CIA group, OX40-Fc/CIA group, and PD-1-Fc + OX40-Fc/CIA group. The pathological changes in mice joints were observed by H&E staining. The proportion of CD4+ T, CD8+ T, CD28+, and CD19+ cells in peripheral blood mononuclear cells (PBMCs) was detected by flow cytometry. Serum inflammatory factors (CRP, IL-2, IL-4, IL-1β, INF-γ) and bone metabolism-related genes (CTX-I, TRACP-5b, BALP) were detected by ELISA assay. Western blotting was applied to measure the NF-κB signaling pathway-related protein (p-IKKβ, p-IκBα, p50) expression in synovial tissue of mice joint. Results Compared with the control group, CIA mice showed significant increases in arthritis score and pathological score. In the CIA group, a marked decrease was identified in the proportion of CD8+ T, CD19+, and CD68+ cells. Additionally, the CIA group was associated with upregulation of secretion of inflammatory factors in serum and expression of bone metabolism-related genes and NF-κB pathway-related proteins. Compared with the CIA group, the same indexes above showed a further aggravation in the PD-1-Fc group while all indexes improved in the OX40-Fc group. Besides, OX40-Fc fusion protein slowed down significantly the further deterioration of CIA mouse pathological process caused by PD-1-Fc fusion protein. Conclusion OX40-Fc fusion protein alleviates PD-1-Fc-aggravated RA by inhibiting inflammatory response. This research provides biological markers with clinical significance for diagnosis and prognosis of RA, as well as offers theoretical and experimental foundation to the new targets for immune intervention.
Highlights
Rheumatoid Arthritis (RA) is a systemic autoimmune disease, with chronic progressive joint lesions as its main symptom [1]
Compared with the collagen-induced arthritis (CIA) group, pathological changes were aggravated in the PD-1-Fc group; the latter group showed that cartilage tissues structure was damaged seriously, chondrocytes were in apoptosis, synovial cells proliferated, and the surface of joints got rough and pathological score increased rapidly
RA is a T cell-mediated autoimmune disease, and PD-1 as well as OX40 costimulation signals plays an important role in regulating the activation of CD4 + T cells
Summary
Rheumatoid Arthritis (RA) is a systemic autoimmune disease, with chronic progressive joint lesions as its main symptom [1]. RA, along with persistent pain, can cause joint deformity and functional loss eventually. It seriously endangers patients’ physical and mental health and affects their quality of life a lot. Western blotting was applied to measure the NF-κB signaling pathway-related protein (p-IKKβ, p-IκBα, p50) expression in synovial tissue of mice joint. Compared with the control group, CIA mice showed significant increases in arthritis score and pathological score. The CIA group was associated with upregulation of secretion of inflammatory factors in serum and expression of bone metabolism-related genes and NF-κB pathway-related proteins. This research provides biological markers with clinical significance for diagnosis and prognosis of RA, as well as offers theoretical and experimental foundation to the new targets for immune intervention
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Computational and Mathematical Methods in Medicine
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
