Atopic dermatitis (AD) results from aberrant Th2 polarization and epidermal barrier impairment. Initially thought to be a Th2 cytokine, IL-9 induces Th9 cells distinct from Th2. Transgenic expression of IL-9 in mice results in asthma. In human, IL-9/IL-9R are significantly increased in AD skin and blood IL-9 levels are correlated with AD severity. Because keratinocytes are the main cells contributing to epidermal barrier, we asked whether IL-9R was expressed in keratinocytes; if so, what immuno-regulatory role it may play. We measured the expression of IL-9R in skin from AD patients and controls and performed in vito studies on the IL-9-treated keratinocytes. The result showed that IL-9R was indeed expressed in keratinocytes but not in fibroblasts. Its expression in keratinocytes was enhanced by IL-4 but not by TGF-beta1. IL-9 induced a moderate production of IL-8 but not CXCL16 or CCL22. IL-9 induced ERK phosphorylation both dose- and time-dependently, but not mTOR, S6K, p38, or STAT3. Pretreatment with U0126 (ERK inhibitor) but not rapamycin (mTOR inhibitor) abrogated the IL-9-mediated IL-8 production. Inhibition of STIM1 abrogated ERK phosphorylation and IL-8 production induced by IL-9. This study concludes how IL-9-STIM1-ERK-IL-8 axis in keratinocyte might play an important role in AD.
Date:
2015-05
Relation:
Journal of Investigative Dermatology. 2015 May;135(Suppl. 1):S90.
