ROLE OF CXCR3 CHEMOKINE RECEPTOR AND ITS LIGANDS IN CERTAIN DISEASES

Abstract

Chemokines are a special family of cytokines whose main function is to control cell migration; they are key players in the innate and adaptive immune responses. Directed chemotaxis of specific leukocyte subpopulations is necessary not only to maintain homeostasis, but also in development of some immunopathological conditions such as cancer, inflammation, infection, allergies and autoimmune disorders. Chemokines are pleiotropic molecules that are involved in physiological and pathophysiological processes. For example, the CXCR3 chemokine receptor is expressed on various cells: activated T and B lymphocytes, natural killers, eosinophils and neutrophils, dendritic cells, fibroblasts, endothelial and epithelial cells. Hence, CXCR3 and its ligands have a wide range of functional activity. CXCR3 ligands are the IFNγ-induced chemokines: CXCL9, CXCL10, CXCL11, and platelet-derived chemokines: CXCL4, CXCL4L1. All the CXCR3 ligands share common angiostatic properties due to lack of the Glu-Leu-Arg (ELR) motif. IFNγ-induced ligands of the CXCR3 are proinflammatory chemokines, they mainly recruit activated T cells and exert an effect on T cell polarization. Due to wide spectrum of biological activity, the ligands of CXCR3 receptor are involved in pathogenesis of various disorders, such as inflammation, infection, cancer, allergies and autoimmune disorders. In this review, we discuss the role of CXCR3 ligands in immunopathogenesis of various diseases, including the results of our studies in chronic hepatitis C, rheumatoid arthritis and pulmonary tuberculosis. Moreover, we have also discussed the potential laboratory diagnostic applicability of the chemokines in various diseases. This review illustrates a universal role of IFNγ-induced chemokines as mediators of immune responses in various diseases. The studies of CXCR3 ligands, their isoforms and receptors, interactions between themselves and with their receptors can provide a significant contribution to our understanding of the chemokine network. Understanding the system of IFNγ-dependent chemokines may have clinical implications, both for diagnostic tasks, and for therapeutic purposes.