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Letters in Drug Design & Discovery

Editor-in-Chief

ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

Application of Agents Against Interferon-Gamma-Dependent Chemokines in Immunotherapy

Author(s): Poupak Fallahi, Silvia Martina Ferrari, Dilia Giuggioli, Clodoveo Ferri and Alessandro Antonelli

Volume 12 , Issue 9 , 2015

Page: [696 - 703] Pages: 8

DOI: 10.2174/1570180812666150414215616

Price: $65

Abstract

The C-X-C chemokine receptor (CXCR)3 and its chemokines (CXCL9, CXCL10, CXCL11) are involved in the pathogenesis of autoimmune disesases. Under the influence of interferon( IFN)γ, the IFNγ-inducible chemokines are secreted by lymphocytes, and by target cells (fibroblasts, epithelial cells, etc). In target tissues, Th1 lymphocytes are recruited; hence IFNγ is enhanced, which stimulates IFNγ-inducible chemokines (CXCL9, CXCL10, CXCL11) secretion reiterating the autoimmune process.

Many studies have evaluated if blockade of CXCR3 or its chemokines have therapeutic significance in autoimmune diseases (for example in thyroid autoimmune disorders, etc).

Peroxisome proliferator-activated receptor (PPAR)γ or -α agonists show a strong inhibitory effect on the expression and production of CXCR3 chemokines in vitro, in various kinds of cells, such as denditric cells, monocytes, macrophages, endothelial and vascular smooth muscle cells, intestinal cells, thyrocytes, fibroblasts, preadipocytes and mesangial cells, and in vivo in animal models.

Further studies are ongoing to explore the use of new molecules that act as antagonists of CXCR3, or block CXCL10, in autoimmune disorders, and many interesting patents have been recently applied. Phase II studies have assessed the efficacy and safety of fully human, monoclonal antibodies to CXCL10, for the treatment of autoimmune disorders (for example rheumatoid arthritis, or ulcerative colitis).

Keywords: CXCR3 chemokines, autoimmune thyroiditis, graves’ disease and ophthalmopathy, inflammatory myopathies, rheumatoid arthritis, type 1 diabetes.

Graphical Abstract

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