Review 10.1586/1744666X.3.3.351 © 2007 Future Drugs Ltd ISSN 1744-666X 351 www.future-drugs.com M echanisms of leukocyte trafficking in allergic diseases: insights into new therapies targeting chemokines and chemokine receptors Masako Toda, Takao Nakamura, Masaharu Ohbayashi, Yoshifumi Ikeda, Maria Dawson, Cho Cho Aye, Dai Miyazaki and Santa Jeremy Ono † † Author for correspondence Emory Eye Center, Emory University School of Medicine, 1365-B Clifton Road, NE Atlanta, Georgia 30322 USA Tel.: +1 404 727 6055 Fax: +1 404 727 6055 sjono@emory.edu KEYWORDS: allergic disease, chemokine, chemokine receptor, leukocyte trafficking Marked inflammatory infiltration by activated leukocytes is a characteristic feature of allergic diseases. Elucidation of the mechanisms of leukocyte trafficking in allergic diseases would identify targets to establish novel anti-inflammatory strategies for treatment of these diseases. Leukocyte trafficking is controlled by tissue-specific expression of chemokines and chemokine receptor expression on the leukocyte surface. Here, we review the role of chemokines and their receptors in leukocyte trafficking to inflammatory sites in allergic diseases and discuss therapeutic strategies targeting chemokine networks for treatment of these diseases. Expert Rev. Clin. Immunol. 3(3), 351–364 (2007) Allergic diseases affect approximately a third of the population of the Western world, and costs associated with these diseases dominate public health budgets. Current treatments are not completely effective and continuing efforts to better understand the molecular bases of allergic responses and to establish new anti-inflammatory drugs for treatment are required [1,2]. In addition to increased IgE production against allergens, allergic diseases are characterized by marked inflammatory infiltration composed of leukocytes, such as T cells, dendritic cells (DCs), mast cells, eosinophils and neutrophils [3,4]. T here is clinical and experimental evidence that tissue-infiltrating leukocytes are in an active state and play a crucial role in initiation and maintenance of allergic inflammation. Therefore, elucidation of the mechanisms of leukocyte trafficking in allergic diseases would be useful for the identification of novel therapeutic targets for these diseases. Traffick- ing of leukocytes into distinct tissues and microenvironments is controlled by tissue-spe- cific expression of chemokines and leukocyte cell-surface expression of their receptors [3–6]. By promoting chemotaxis and integrin activa- tion, chemokines and their receptors control leukocyte trafficking in conjunction with sur- face-adhesion molecules [3–6]. Chemokines are a cytokine superfamily of low-molecular- weight proteins. Chemokines are divided into four subclasses based on the arrange- ment of the N-terminal cysteine residues: CXC chemokines (termed CXC ligands [CXCLs]); CC chemokines (CCLs); C chemokines (XCLs); and CX 3 C chemok- ines (CX 3 CLs) [6,7]. Each family of chemok- ines interacts with a reciprocal family of G-protein-coupled receptors (GPCRs) with seven-transmembrane domain. To date, over 40 human chemokine ligands and 18 chemo- kine receptors have been identified (TABLE 1). Significant effort has been invested in search- ing for the axes of chemokines and their receptors involved in leukocyte trafficking CONTENTS T cells Dendritic cells Mast cells Eosinophils Neutrophils Expert commentary & five-year view Key issues References Affiliations For reprint orders, please contact reprints@future-drugs.com