title: Epidermal ablation of Dlx3 is linked to IL-17-associated skin inflammation.
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.
authors.affiliation: Developmental Skin Biology Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Joonsung
authors.initials: J
authors.lastname: Hwang
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Kita
authors.forename: Hyouk-Soo
authors.initials: HS
authors.lastname: Kwon
authors.forename: Eung Ho
authors.initials: EH
authors.lastname: Choi
authors.forename: Seung Hun
authors.initials: SH
authors.lastname: Lee
authors.forename: Mark C
authors.initials: MC
authors.lastname: Udey
authors.forename: Maria I
authors.initials: MI
authors.lastname: Morasso
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D016207:Cytokines / Q000096:biosynthesis; D003872:Dermatitis / Q000209:etiology* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D004817:Epidermis / Q000276:immunology / Q000473:pathology; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology*; D006801:Humans; D006965:Hyperplasia; D018836:Inflammation Mediators / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism*; D015603:Keratinocytes / Q000276:immunology / Q000473:pathology; D007962:Leukocytes / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D011247:Pregnancy; D058504:Th17 Cells / Q000276:immunology / Q000473:pathology; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics / Q000276:immunology*
chemical_list: D016207:Cytokines; C088334:Distal-less homeobox proteins; D018398:Homeodomain Proteins; D018836:Inflammation Mediators; D020381:Interleukin-17; D014157:Transcription Factors