**4. Acknowledgments**

This work was partly supported by grants from the Ministry of Education, Science, Technology, Sports and Culture of Japan Science (to H.Y and Y.M) and a Takeda Foundation research grant (to H.Y.).

### **5. References**


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**3** 

*Japan* 

**The Roles of Th2-Type Cytokines in the** 

*1Division of Medical Biochemistry, Department of Biomolecular Sciences* 

Atopic dermatitis (AD) is a chronic, relapsing, highly pruritic inflammatory skin disease (1, 2). Analyses of the cytokine expression profile in skin lesions of AD patients show that the Th2-type immune response is dominant in AD inflammation (3, 4). Interleukin-4 (IL-4), IL-5, and IL-13 are signature cytokines of the Th2-type immune response. Expression of IL-4 and IL-13 is significantly high in acute lesions of AD skin; however, it is downregulated in chronic lesions. In contrast, expression of IL-5 is more elevated in chronic lesions than in acute lesions. High expression of IL-4, IL-5, and IL-13 in AD skins leads to high serum levels of IgE and eosinophilia, typical clinical features of AD. In addition to IL-5, expression of interferon-γ (IFN-γ) and IL-12 is elevated in chronic skin lesions of AD. IFN-γ and IL-12 are signature cytokines of Th1-type immune response. It has remained

Based on observations of the predominant Th2-type immune responses in AD patients, many studies using model mice or involving genetic association have been performed to investigate the role played by Th2-type cytokines in the pathogenesis of AD. It is hoped that Th2-type cytokines will prove to be good targets to develop therapeutic agents for AD. In this chapter, we focus on these topics; we do not review the details of the structures, the signal pathways, or the biological functions of these Th2-type cytokines.

Animal models are useful to understand the pathogenesis of AD and to develop therapeutic agents for AD. Among various species, mouse models have been primarily used, because genetically manipulated mice are available. Mouse models of AD can be categorized into three groups (2): (1) mice that spontaneously develop AD-like skin lesions, (2) mice epicutaneously sensitized with allergens, and (3) genetically engineered mice. It has been reported that several AD model mice that spontaneously develop AD-like skin lesions such as Nc/Nga mice (11) and DS-Nh mice (12) show a Th2-type–dominant immune milieu, suggesting that Th2-type cytokines are involved in pathogenesis in these mice. However, the situation is more complex, because it has been demonstrated that Nc/Nga mice deficient

**1. Introduction** 

unclear why this immune milieu change occurs.

**2. Th2-type cytokines in model mice** 

Please refer to other articles regarding with these subjects (5-10).

**Pathogenesis of Atopic Dermatitis** 

Kenji Izuhara1, Hiroshi Shiraishi1, Shoichiro Ohta2,

*2Department of Laboratory Medicine, Saga Medical School* 

Kazuhiko Arima1 and Shoichi Suzuki1

*Investigation; a Journal of Technical Methods and Pathology*, Vol. 82, No.6, (June 2002), pp. 789-794, ISSN 0023-6837

