CCL17/TARC in autoimmunity and inflammation - not just a T-cell chemokine.

Chemokine (C-C) ligand 17 (CCL17) was first identified as thymus- and activation- regulated chemokine (TARC), when it was found to be constitutively expressed in the thymus and identified as a T-cell chemokine. This chemo-attractant molecule has subsequently been found at elevated levels in a range of autoimmune and inflammatory diseases, as well as in cancer. CCL17 is a CCR4 ligand, with CCL22 being the other major ligand and, as CCR4 is highly expressed on helper T cells, CCL17 can play a role in T-cell driven diseases, usually considered to be via its chemotactic activity on Th2 cells; however, given that CCR4 is also expressed by other cell types and there is elevated expression of CCL17 in many diseases, a broader CCL17 biology is suggested. In this review, we summarise the biology of CCL17 and its regulation, and its potential contribution to the pathogenesis of various preclinical models. Reference is made, for example, to recent literature indicating a role for CCL17 in the control of pain as part of a GM-CSF/CCL17 pathway in lymphocyte-independent models and thus not as a T-cell chemokine. The review also discusses the potential for CCL17 to be a biomarker and a therapeutic target in human disorders.