Chemokine (C–X–C motif) ligand (CXCL)10 in autoimmune diseases

• The involvement of CXCR3 and CXCL10 in many autoimmune diseases is demonstrated.
• High CXCL10 level in peripheral liquids is a marker of host Th1 immune response.
• IFNγ/TNFα stimulates a variety of cells to produce CXCL10 recruiting Th1 lymphocytes.
• Studies are evaluating CXCL10 as a novel therapeutic target in autoimmune diseases.

(C–X–C motif) ligand (CXCL)10 (CXCL10) belongs to the ELR− CXC subfamily chemokine. CXCL10 exerts its function through binding to chemokine (C–X–C motif) receptor 3 (CXCR3), a seven trans-membrane receptor coupled to G proteins. CXCL10 and its receptor, CXCR3, appear to contribute to the pathogenesis of many autoimmune diseases, organ specific (such as type 1 diabetes, autoimmune thyroiditis, Graves' disease and ophthalmopathy), or systemic (such as rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, mixed cryoglobulinemia, Sjögren syndrome, or systemic sclerosis).The secretion of CXCL10 by cluster of differentiation (CD)4 +, CD8 +, natural killer (NK) and NK-T cells is dependent on interferon (IFN)-γ, which is itself mediated by the interleukin-12 cytokine family. Under the influence of IFN-γ, CXCL10 is secreted by several cell types including endothelial cells, fibroblasts, keratinocytes, thyrocytes, preadipocytes, etc. Determination of high level of CXCL10 in peripheral fluids is therefore a marker of host immune response, especially T helper (Th)1 orientated T-cells. In tissues, recruited Th1 lymphocytes may be responsible for enhanced IFN-γ and tumor necrosis factor-α production, which in turn stimulates CXCL10 secretion from a variety of cells, therefore creating an amplification feedback loop, and perpetuating the autoimmune process.Further studies are needed to investigate interactions between chemokines and cytokines in the pathogenesis of autoimmune diseases and to evaluate whether CXCL10 is a novel therapeutic target in various autoimmune diseases.