OX40-Fc Fusion Protein Alleviates PD-1-Fc-Aggravated Rheumatoid Arthritis by Inhibiting Inflammatory Response

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.

Development of HEK293T-produced recombinant receptor-Fc proteins as potential candidates against canine distemper virus

“…Since the first description in 1989 of CD4-Fc-fusion antagonists that inhibit human immune deficiency virus entry into T cells, Fc-fusion proteins have been intensely investigated for their effectiveness to curb a range of pathologies. In the treatment of human diseases, Fc-fusion strategies have been used in therapy including experimental and clinical drugs (21)(22)(23). Fusion proteins based on the immunoglobulin Fc domain show the ability to facilitate protein expression and enable easy purification of recombinant protein by protein A chromatography (24).…”

Synovial Macrophages Expression of OX40L Is Required for Follicular Helper T Cells Differentiation in the Joint Microenvironment

“…T lymphocytes in synovial fluid and synovial tissue from RA patients express OX40, and OX40L is expressed on sub-lining cells in synovial tissue [ 9 ]. OX40-Fc fusion protein alleviates PD-1-Fc-exacerbated RA by suppressing the inflammatory response [ 10 ]. In addition, OX40 plays a pathogenic role in the development of autoimmune arthritis as an alternative co-stimulator of CD4 + CD28 − T cells, suggesting it as a potential target for immunomodulatory therapy in RA [ 11 ].…”

Retracted: OX40‐Fc Fusion Protein Alleviates PD‐1‐Fc‐Aggravated Rheumatoid Arthritis by Inhibiting Inflammatory Response

“…This article has been retracted by Hindawi following an investigation undertaken by the publisher [ 1 ]. This investigation has uncovered evidence of one or more of the following indicators of systematic manipulation of the publication process: Discrepancies in scope Discrepancies in the description of the research reported Discrepancies between the availability of data and the research described Inappropriate citations Incoherent, meaningless and/or irrelevant content included in the article Peer-review manipulation …”

“…This article has been retracted by Hindawi following an investigation undertaken by the publisher [1]. This investigation has uncovered evidence of one or more of the following indicators of systematic manipulation of the publication process:…”