| First Author | Floudas A | Year | 2017 |
| Journal | J Immunol | Volume | 199 |
| Issue | 2 | Pages | 707-717 |
| PubMed ID | 28615416 | Mgi Jnum | J:251376 |
| Mgi Id | MGI:6100735 | Doi | 10.4049/jimmunol.1602185 |
| Citation | Floudas A, et al. (2017) IL-17 Receptor A Maintains and Protects the Skin Barrier To Prevent Allergic Skin Inflammation. J Immunol 199(2):707-717 |
| abstractText | Atopic dermatitis (AD) is a common inflammatory skin disease affecting up to 20% of children and 3% of adults worldwide and is associated with dysregulation of the skin barrier. Although type 2 responses are implicated in AD, emerging evidence indicates a potential role for the IL-17A signaling axis in AD pathogenesis. In this study we show that in the filaggrin mutant mouse model of spontaneous AD, IL-17RA deficiency (Il17ra(-/-) ) resulted in severe exacerbation of skin inflammation. Interestingly, Il17ra(-/-) mice without the filaggrin mutation also developed spontaneous progressive skin inflammation with eosinophilia, as well as increased levels of thymic stromal lymphopoietin (TSLP) and IL-5 in the skin. Il17ra(-/-) mice have a defective skin barrier with altered filaggrin expression. The barrier dysregulation and spontaneous skin inflammation in Il17ra(-/-) mice was dependent on TSLP, but not the other alarmins IL-25 and IL-33. The associated skin inflammation was mediated by IL-5-expressing pathogenic effector Th2 cells and was independent of TCRgammadelta T cells and IL-22. An absence of IL-17RA in nonhematopoietic cells, but not in the hematopoietic cells, was required for the development of spontaneous skin inflammation. Skin microbiome dysbiosis developed in the absence of IL-17RA, with antibiotic intervention resulting in significant amelioration of skin inflammation and reductions in skin-infiltrating pathogenic effector Th2 cells and TSLP. This study describes a previously unappreciated protective role for IL-17RA signaling in regulation of the skin barrier and maintenance of skin immune homeostasis. |
