Expression and Function of CCL17 in Atopic Dermatitis

Chemokines are a superfamily of potent leukocyte chemoattractant cytokines with a molecular weight of 8-12 kDa. Historically, many chemokines had more than one name until the 1999 Keystone Symposium on Chemokines, when a new nomenclature was introduced (Zlotnik & Yoshie, 2000). Chemokines have been subdivided into four subfamilies on the basis of the position of either one or two cysteine residues located near the N-terminus of the protein and an L (ligand) was added (CXCL, CCL, CL and CXXXCL) to designate all chemokines as ligands of their respective receptors (R). The chemokine network comprises about 50 chemokines, as well as 20 classical (10 CCRs, 7 CXCRs, two XCR and a single CX3CR) and 3 atypical chemokine receptors (Duffy antigen receptor for chemokines = DARC, CC-X-chemokine receptor (CCX-CKR), and the D6 molecule) (Cyster, 2005; Comerford & McColl, 2011; Hansell & Nibbs, 2007; Ransohoff, 2009; Sallusto & Baggiolini, 2008). Many ligands bind multiple receptors, although each of them bind in a slightly different way, thereby inducing distinct downstream responses. The timing and venue of specific ligand-receptor interactions determines the nature of various biological processes. Although their best known function is the regulation of leukocyte migration, chemokines also enhance cell adhesion or costimulation, and stimulate myelopoiesis, tumor growth or angiogenesis (Ransohoff, 2009; Sallusto & Baggiolini, 2008; Viola & Luster, 2008). In addition, chemokines participate in the organization of the microenvironmental architecture of primary and secondary lymphoid organs during physiological and pathological conditions (Cyster, 2005). Importantly, a defined subset of chemokines and their receptors drive certain inflammatory immune responses to protect the body against microbial and environmental pathogens. Dysregulation of such chemokines may contribute to the pathogenesis of inflammatory diseases, like acute respiratory distress syndrome, multiple sclerosis, inflammatory bowel diseases, atherosclerosis, or rheumatoid arthritis (Charo & Ransohoff, 2006). Furthermore, chemokines produced in barrier organs are known to