Abstract
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 γδ 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.
| Original language | English |
|---|---|
| Pages (from-to) | 11566-11571 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 108 |
| Issue number | 28 |
| DOIs | |
| Publication status | Published - 2011 Jul 12 |
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Epidermal ablation of Dlx3 is linked to IL-17-associated skin inflammation. / Hwang, Joonsung; Kita, Ryosuke; Kwon, Hyouk Soo; Choi, Eung Ho; Lee, Seung Hun; Udey, Mark C.; Morasso, Maria I.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, No. 28, 12.07.2011, p. 11566-11571.Research output: Contribution to journal › Article
TY - JOUR
T1 - Epidermal ablation of Dlx3 is linked to IL-17-associated skin inflammation
AU - Hwang, Joonsung
AU - Kita, Ryosuke
AU - Kwon, Hyouk Soo
AU - Choi, Eung Ho
AU - Lee, Seung Hun
AU - Udey, Mark C.
AU - Morasso, Maria I.
PY - 2011/7/12
Y1 - 2011/7/12
N2 - 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 γδ 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.
AB - 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 γδ 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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UR - http://www.scopus.com/inward/citedby.url?scp=79960978246&partnerID=8YFLogxK
U2 - 10.1073/pnas.1019658108
DO - 10.1073/pnas.1019658108
M3 - Article
VL - 108
SP - 11566
EP - 11571
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 28
ER -