| First Author | Bouchaud G | Year | 2013 |
| Journal | J Exp Med | Volume | 210 |
| Issue | 10 | Pages | 2105-17 |
| PubMed ID | 24019554 | Mgi Jnum | J:204085 |
| Mgi Id | MGI:5529570 | Doi | 10.1084/jem.20130291 |
| Citation | Bouchaud G, et al. (2013) Epidermal IL-15Ralpha acts as an endogenous antagonist of psoriasiform inflammation in mouse and man. J Exp Med 210(10):2105-17 |
| abstractText | Stromal cells at epithelial surfaces contribute to innate immunity by sensing environmental danger signals and producing proinflammatory cytokines. However, the role of stromal cells in controlling local inflammation is unknown. We show that endogenous soluble IL-15 receptor alpha (IL-15Ralpha) derived from epidermal stroma, notably keratinocytes, protects against dendritic cell/IL-15-mediated, T cell-driven skin inflammation in vivo, and is relevant to human psoriasis. Selective lack of IL-15Ralpha on stromal epidermal cells exacerbated psoriasiform inflammation in animals. Epidermal IL-15Ralpha was shed by keratinocytes via proteolytic cleavage by matrix metalloproteinases upon stimulation with proinflammatory cytokines to counteract IL-15-induced proliferation of IL-17(+) alphabeta and gammadelta T cells and production of TNF, IL-23, IL-17, and IL-22 during skin inflammation. Notably, administration of soluble IL-15Ralpha was able to repress secretion of IL-1beta, IL-6, and TNF by keratinocytes, dampen expansion of IL-17(+) alphabeta and gammadelta T cells in vivo, and prevent psoriasis in two mouse models, including human xenograft AGR mice. Serum levels of soluble IL-15Ralpha negatively correlated with disease severity, and levels rose upon successful treatment of psoriasis in patients. Thus, stressed epidermal stromal cells use soluble IL-15Ralpha to dampen chronic inflammatory skin disease. |
