IL-23- and IL-17A-producing CD4+ T cell (Th17 cell) axis plays a crucial role in the development of chronic inflammatory diseases. In addition, it has been demonstrated that Th17 cells and their cytokines such as IL-17A and IL-17F are involved in the pathogenesis of severe asthma. Recently, IL-22, an IL-10 family cytokine that is produced by Th17 cells, has been shown to be expressed at the site of allergic airway inflammation and to inhibit allergic inflammation in mice. In addition to Th17 cells, innate lymphoid cells also produce IL-22 in response to allergen challenge. Functional IL-22 receptor complex is expressed on lung epithelial cells, and IL-22 inhibits cytokine and chemokine production from lung epithelial cells. In this paper, we summarize the recent progress on the roles of IL-22 in the regulation of allergic airway inflammation and discuss its therapeutic potential in asthma. 1. Introduction Asthma is a chronic inflammatory disease that is accompanied by intense eosinophilic infiltration, goblet cell hyperplasia, and airway hyperreactivity (AHR) [1]. In atopic asthma patients, it is well established that these features are mediated by antigen-specific Th2 cells and their cytokines including IL-4, IL-5, and IL-13 [2, 3]. In addition, several lines of evidence have shown that not only Th2 cell-derived cytokines but also Th17 cell-derived cytokines such as IL-17A and IL-17F are expressed in the airways in severe asthma patients, and that the levels of IL-17A and IL-17F in the airways are correlated with the severity of asthma, suggesting the involvement of Th17 cell-derived cytokines in the pathogenesis of severe asthma [4, 5]. Moreover, we and others have shown that Th17 cells are involved in the development of antigen-induced airway inflammation in murine asthma models [6–8]. Interestingly, recent studies have shown that IL-22, one of Th17 cell-derived cytokines, is detected in bronchoalveolar lavage fluid (BALF) in murine asthma models [8, 9]. Furthermore, it has been reported that the levels of IL-22 mRNA are increased in peripheral blood mononuclear cells in asthma patients [10, 11], and that the levels of IL-22 in sera tend to correlate with the severity of asthma [12]. In this paper, we briefly summarize the roles of IL-22 in the regulation of allergic inflammation in asthma. 2. IL-22 and IL-22 Receptor IL-22 is an IL-10 family cytokine that is originally identified from IL-9-stimulated T lymphoma cells and designated as IL-TIF (IL-10-related T cell-derived inducible factor) [13]. Functional IL-22 receptor consists of IL-22R1 and
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