REVIEW DOI: 10.3904/kjim.2011.26.1.8 REVIEW Prostaglandin D2 and TH2 Inflammation in the Pathogenesis of Bronchial Asthma Masafumi Arima1 and Takeshi Fukuda2 1Department of Developmental Genetics (H2), Chiba University Graduate School of Medicine, Chiba; 2Department of Pulmonary Medicine and Clinical Immunology, Dokkyo University School of Medicine, Tochigi, Japan Prostaglandin D2 (PGD2) is a major prostanoid, produced mainly by mast cells, in allergic diseases, including bronchial asthma. PGD2-induced vasodilatation and increased permeability are well-known classical effects that may be involved in allergic inflammation. Recently, novel functions of PGD2 have been identified. To date, D prostanoid receptor (DP) and chemoattractant receptor homologous molecule expressed on TH2 cells (CRTH2) have been shown to be major PGD2-related receptors. These two receptors have pivotal roles mediating allergic diseases by regulating the functions of various cell types, such as TH2 cells, eosinophils, basophils, mast cells, dendritic cells, and epithelial cells. This review will focus on the current understanding of the roles of PGD2 and its metabolites in TH2 inflammation and the pathogenesis of bronchial asthma. (Korean J Intern Med 2011;26:8-18) Keywords: Basophils; Asthma; Eosinophils; Mast cells; Prostaglandins; TH2 cells INTRODUCTION Asthma is characterized by chronic inflammation of the airways, associated with inflammatory cells, including eosinophils, mast cells, basophils, macrophages, and T helper (TH) cells. These cells are involved in development of airway hyperresponsiveness (AHR), bronchoconstric- tion, mucus secretion, and remodeling by releasing inflammatory mediators, such as chemokines, growth fac- tors, lipid mediators, and chemical mediators. Then, the complex pathogenesis of asthma is contributed to by vari- ous cellular responses, based on the dysregulated interac- tion between the innate and adaptive immune systems. Recent evidence suggests that prostaglandin D2 (PGD2), a major prostanoid, may play an important role in orches- trating interactions between mast cells, TH2 cells, eosinophils, and dendritic cells. TH2 immune response in asthma Allergic diseases are characterized by elevated serum immunoglobulin (Ig) E levels and hypersensitivity to nor- mally innocuous antigens as allergens. A particular aller- gen first encounters antigen-processing cells (APC), such as dendritic cells or macrophages, directly. The allergen captured by the APC is processed and presented to CD4+ T cells. CD4+ T cells are polarized into distinct types of TH cells. Major TH cell subsets include TH1, TH2, and TH17, and also recently discovered TH9 and TFH cells. Each TH cell subset expresses a characteristic cytokine profile that generates a characteristic inflammatory response in aller- gic diseases, such as bronchial asthma. Among these TH cells, TH2 cells are believed to play a critical pathogenic role in allergic inflammation. TH2 cells produce cytokines, interleukin (IL)-4, IL-5, IL-6, IL-9, and IL-13, although they may also result from other cell types. Patients with allergic asthma have eosinophilic inflammation in the lung, in parallel with increased TH2 cytokines, as well as elevated serum IgE. IL-4 and IL-13 are representative TH2-type cytokines that play a crucial role in human aller- gic disease. IL-4 promotes differentiation and prolifera- tion in TH2 cells, whereas IL-13 mediates AHR and mucus hyperproduction [1,2]. IL-5 is a cytokine that is highly spe- cific to eosinophil activation and recruitment and con- Correspondence to Masafumi Arima, M.D., Ph.D. Department of Developmental Genetics (H2), Chiba University Graduate School of Medicine, Inohana 1-8-1, Chuo-ku, Chiba 260-8670, Japan Tel: 81-43-226-2182, Fax: 81-43-226-2183, E-mail: masaarima@faculty.chiba-u.jp