期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 108, 期 28, 页码 11566-11571出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1019658108
关键词
barrier function; psoriasis; inflammatory diseases; homeobox transcription factor; mouse model
资金
- NIAMS
- Center for Cancer Research of the NCI at the National Institutes of Health
In an effort to understand the role of Distal-less 3 (Dlx3) in cutaneous biology and pathophysiology, we generated and characterized a mouse model with epidermal ablation of Dlx3. K14cre;Dlx3(Kin/f) mice exhibited epidermal hyperproliferation and abnormal differentiation of keratinocytes. Results from subsequent analyses revealed cutaneous inflammation that featured accumulation of IL-17-producing CD4(+) T, CD8(+) T, and gamma delta T cells in the skin and lymph nodes of K14cre;Dlx3(Kin/f) mice. The gene expression signature of K14cre; Dlx3(Kin/f) skin shared features with lesional psoriatic skin, and Dlx3 expression was markedly and selectively decreased in psoriatic skin. Interestingly, cultured Dlx3 null keratinocytes triggered cytokine production that is potentially linked to inflammatory responses in K14cre; Dlx3(Kin/f) mice. Thus, Dlx3 ablation in epidermis is linked to altered epidermal differentiation, barrier development, and IL-17-associated skin inflammation. This model provides a platform that will allow the systematic exploration of the contributions of keratinocytes to cutaneous inflammation.
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