2015年顧家綺老師實驗室論文發表
 

2015年顧家綺老師實驗室論文發表--李宗霖

An Alternatively Spliced IL-15 Isoform Modulates Abrasion-Induced Keratinocyte Activation
Tsung-Lin Lee1,5, Mei-Ling Chang2,5, Yu-Jei Lin1, Ming-Hsun Tsai1, Yi-Hsuan Chang1, Che-Ming Chuang1,
Yun Chien1, Tomasz Sosinowski3, Chih-HsiuWang1, Yi-Yuan Chen1, Chien-Kuo Lee1, Jau-Shiuh Chen4,
Li-Fang Wang4, John T. Kung2 and Chia-Chi Ku1

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-15DE7, 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-15DE7 in
WT skin prevented abrasion-induced epidermal thickening, blocked the accumulation of nuclear antigen Ki67þ
cells in the basal and the suprabasal cell layers, increased loricrin expression, and also increased keratinocyte
CXCL1 and G-CSF production. IL-15DE7 also profoundly blocked neutrophil infiltration in SDS- or immiquimod
(IMQ)-treatedWT skin. Recombinant IL-15DE7 failed to activate STAT-5 and its downstream target bcl-2 expression.
Our study points to IL-15DE7 as a potential therapeutic agent for treating neutrophilia-associated inflammatory
skin disorders.
Journal of Investigative Dermatology advance online publication, 19 February 2015; doi:10.1038/jid.2015.17