IL-13R alpha 2 Has a Protective Role in a Mouse Model of Cutaneous Inflammation

• Published in: The Journal of immunology (1950) 2010-12, Vol.185 (11), p.6802-6808
• Main Authors: Sivaprasad, Umasundari, Warrier, Manoj R, Gibson, Aaron M, Chen, Weiguo, Tabata, Yasuhiro, Bass, Stacey A, Rothenberg, Marc E, Khurana Hershey, Gurjit K
• Format: Article
• Language: English
• ISSN: 0022-1767
• DOI: 10.4049/jimmunol.1002118

IL-13 is expressed in lesions of atopic dermatitis (AD) and has been associated with increased disease severity. IL-13 has two cognate receptors: IL-13R alpha 1 and IL-13R alpha 2. Although IL-13R alpha 2 expression is known to be induced in response to IL-13 in keratinocytes, its function in AD has never been evaluated. We characterized the loss of skin barrier function and the development of cutaneous inflammation in IL-13R alpha 2-null versus wild-type BALB/c mice following an epicutaneous allergen-sensitization/challenge model that shares similarities with human AD. Mice lacking IL-13R alpha 2 had significantly increased transepidermal water loss, cutaneous inflammation, peripheral eosinophilia, and IgG1 and IgE levels compared with wild-type mice. The rate of resolution of the cutaneous inflammation was not significantly altered in the IL-13R alpha 2-null mice. IL-13 induced expression of IL-13R alpha 2 in keratinocyte cell lines and primary human keratinocytes. Depletion of IL-13R alpha 2 in a keratinocyte cell line resulted in increased STAT6 signaling in response to IL-13. In conclusion, IL-13R alpha 2 serves a protective role in the pathogenesis of allergic inflammation and loss of skin barrier function in a mouse model of AD, suggesting that it may be an important endogenous regulator of IL-13-induced cutaneous inflammation in humans.