Epidermal ablation of Dlx3 is linked to IL-17-associated skin inflammation

Joonsung Hwang, Ryosuke Kita, Hyouk Soo Kwon, Eung Ho Choi, Seung Hun Lee, Mark C. Udey, Maria I. Morasso

Research output: Contribution to journalArticle

29 Citations (Scopus)

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 languageEnglish
Pages (from-to)11566-11571
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number28
DOIs
Publication statusPublished - 2011 Jul 12

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Interleukin-17
Inflammation
Skin
Keratinocytes
Transcriptome
Epidermis
Lymph Nodes
Cytokines
T-Lymphocytes

All Science Journal Classification (ASJC) codes

  • General

Cite this

Hwang, Joonsung ; Kita, Ryosuke ; Kwon, Hyouk Soo ; Choi, Eung Ho ; Lee, Seung Hun ; Udey, Mark C. ; Morasso, Maria I. / Epidermal ablation of Dlx3 is linked to IL-17-associated skin inflammation. In: Proceedings of the National Academy of Sciences of the United States of America. 2011 ; Vol. 108, No. 28. pp. 11566-11571.
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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.",
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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 journalArticle

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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.

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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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