| First Author | Lee TL | Year | 2015 |
| Journal | J Invest Dermatol | Volume | 135 |
| Issue | 5 | Pages | 1329-1337 |
| PubMed ID | 25615554 | Mgi Jnum | J:220593 |
| Mgi Id | MGI:5635717 | Doi | 10.1038/jid.2015.17 |
| Citation | Lee TL, et al. (2015) An Alternatively Spliced IL-15 Isoform Modulates Abrasion-Induced Keratinocyte Activation. J Invest Dermatol 135(5):1329-37 |
| abstractText | In a routine phenotype-driven screen, we identified a point mutation in exon 7 of the IL-15 gene in Pedigree 191 (deficient memory (DM)) of N-ethyl-N-nitrosourea mutagenized mice. The DM epidermis expressed an alternatively spliced IL-15 mRNA isoform, IL-15DeltaE7, and a wild-type (WT) IL-15 isoform at comparable levels. Mechanical stimulation of DM skin or DM skin graft transplanted onto the WT host resulted in reduced keratinocyte activation and inhibition of neutrophil infiltration into the dermis, demonstrating that DM keratinocytes produced less inflammatory response to external stimulation. Ectopic expression of IL-15DeltaE7 in WT skin prevented abrasion-induced epidermal thickening, blocked the accumulation of nuclear antigen Ki67(+) cells in the basal and the suprabasal cell layers, increased loricrin expression, and also increased keratinocyte CXCL1 and G-CSF production. IL-15DeltaE7 also profoundly blocked neutrophil infiltration in SDS- or immiquimod (IMQ)-treated WT skin. Recombinant IL-15DeltaE7 failed to activate STAT-5 and its downstream target bcl-2 expression. Our study points to IL-15DeltaE7 as a potential therapeutic agent for treating neutrophilia-associated inflammatory skin disorders. |
