Understanding the Pleiotropic Effects of Cxcl10/Ip-10 in the Immunopathogenesis of Inflammatory Rheumatic Diseases: Implications for Better Understanding Disease Mechanisms Publisher Pubmed



Rokni M^{1, 2} ; Khomeijanifarahani M³ ; Soltani T³ ; Jamshidi A³ ; Mahmoudi M^{3, 4} ; Farhadi E^{3, 4} Show Affiliations
Source: International Immunopharmacology Published:2025

Abstract

Chemokines play a critical role in immune responses, acting as chemotactic factors and effectors in different immune processes. CXCL10/IFN-gamma-inducible protein 10 (IP-10) is an inflammatory chemokine that regulates immune cell activation and recruitment by binding to its receptor CXCR3. Additionally, CXCL10 inhibits angiogenesis by interacting with endothelial cells (ECs). In the context of inflammatory rheumatic diseases, CXCL10 influences multiple pathways including chemotaxis, angiostasis, bone destruction, joint inflammation, and regulation of fibroblast-like synoviocyte properties. High levels of CXCL10 have been detected in the serum and tissues of individuals with autoimmune conditions like systemic sclerosis (SSc), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and among others (ankylosing spondylitis, Behcet's syndrome). The CXCL10 may inhibit fibroblast recruitment after tissue injury, delaying wound healing; inhibiting angiogenesis, and uncontrolled pulmonary fibrosis in SSc. In RA disease, the CXCL10-CXCR3 axis could increase the inflammatory cell infiltration, including T lymphocytes and macrophages, into inflamed joints, enhancing arthritis severity and bone and cartilage destruction. The interaction between CXCR3 and ligand-CXCL10 on directing the CD4+ T lymphocytes polarization and observed that CXCL10 skew T lymphocytes polarization into Th1/Th17 effector cells that could lead to an increase in the inflammatory responses in the SLE. This study aims to explore the role of CXCL10 in rheumatic diseases and its potential as both a therapeutic target and a biomarker for these conditions. Understanding the involvement of CXCL10 in the immunopathogenesis of inflammatory rheumatic diseases may provide valuable insights for the development of targeted therapies and diagnostic strategies. © 2025 Elsevier B.V.