**11. Summary and future direction**

NSAIDs, which block the production of all prostanoids, usually have limited effects on AD (Kabashima and Miyachi, 2004) and therefore have not been given so much attention as a potential therapeutic agent. However, the analysis using the receptor knockout mice and receptor specific drugs has revealed new unexpected roles of prostanoids in the immune systems. In addition, signaling from even the same receptor can produce the opposite effect depending on the context, such as the Th1 modulating effect generated through EP2/EP4 signaling (Yao et al., 2009). Therefore, it would be necessary to reconsider the role of prostanoids in the development of AD. It is also important to correlate these immunomodulatory actions of prostanoids found in mice to their actions in immune diseases of humans. Currently, CRTH2 antagonists are on their way to being used in clinical applications for AD or asthma (Ulven and Kostenis., 2010). Further analysis of the role of each prostanoid receptor has great potential in leading to a new therapeutic target for AD.

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**6** 

*1USA 2,3Germany* 

**Expression and Function of** 

**CCL17 in Atopic Dermatitis** 

*1Department of Microbiology and Immunobiology* 

*for Environmental Medicine, Düsseldorf 3Department of Dermatology and Allergy University of Bonn Medical Center, Bonn* 

*Division of Immunology, Harvard Medical School, Boston 2Molecular Immunology, IUF – Leibniz Research Institute* 

Susanne Stutte1, Nancy Gerbitzki2, Natalija Novak3 and Irmgard Förster2

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

**1. Introduction** 

inflammation through Th1 cell differentiation and Th17 cell expansion. Nat Med *15*, 633-640.

Yoshimura-Uchiyama, C., Iikura, M., Yamaguchi, M., Nagase, H., Ishii, A., Matsushima, K., Yamamoto, K., Shichijo, M., Bacon, K.B., and Hirai, K. (2004). Differential modulation of human basophil functions through prostaglandin D2 receptors DP and chemoattractant receptor-homologous molecule expressed on Th2 cells/DP2. Clin Exp Allergy *34*, 1283-1290.
