Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 108, Issue 28, Pages 11566-11571Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1019658108
Keywords
barrier function; psoriasis; inflammatory diseases; homeobox transcription factor; mouse model
Categories
Funding
- NIAMS
- Center for Cancer Research of the NCI at the National Institutes of Health
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available