title: Increased Th2 activity and diminished skin barrier function cooperate in allergic skin inflammation.
abstract: Atopic dermatitis (AD) is a chronic inflammatory skin disease induced by a complex interaction between susceptibility genes encoding skin barrier components and environmental allergen exposure that results in type 2 cytokine production. Although genetic lesions in either component can be risk factors for disease in patients, whether these pathways interact in the development of AD is not clear. To test this, we mated mice with T-cell specific expression of constitutively active Stat6 (Stat6VT) that spontaneously develop allergic skin inflammation with Flaky tail (Ft) mice that have mutations in Flg and Tmem79 genes that each affect skin barrier function. Our results demonstrate that over 90% of the Stat6VT transgenic mice carrying the Ft alleles (Stat6VTxFt-/-) develop severe atopic dermatitis lesions by 3-5 months of age, compared with only 40% of Stat6VT mice that develop disease by 6-7 months of age. Further, histopathological analysis of skin tissues from Stat6VTxFt-/-mice revealed extensive thickening of the dermis with increased inflammatory infiltrates as compared with Stat6VT mice. Our study suggests that skin barrier defects and altered Th2 responses independently cooperate in the pathogenesis of allergic skin inflammation, similar to effects observed in patients with AD.
authors: Department of Pediatrics and Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.
authors: Sarita
authors: S
authors: Sehra
authors: Department of Pediatrics and Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.|Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors: Purna
authors: P
authors: Krishnamurthy
authors: Department of Pediatrics and Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.|Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors: Byunghee
authors: B
authors: Koh
authors: Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors: Hong-Ming
authors: HM
authors: Zhou
authors: Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors: Lee
authors: L
authors: Seymour
authors: Department of Pediatrics and Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.
authors: Nahid
authors: N
authors: Akhtar
authors: Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN, USA.|Department of Pharmacology and Toxicology, Wright State University, Dayton, OH, USA.
authors: Jeffrey B
authors: JB
authors: Travers
authors: Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors: Matthew J
authors: MJ
authors: Turner
authors: Department of Pediatrics and Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA. mkaplan2@iupui.edu.|Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA. mkaplan2@iupui.edu.
authors: Mark H
authors: MH
authors: Kaplan
mesh_terms: D000818:Animals; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D000091344:Filaggrin Proteins; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D010539:Permeability; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics; D050800:STAT6 Transcription Factor / Q000235:genetics; D012867:Skin / Q000276:immunology* / Q000473:pathology* / Q000503:physiopathology; D018418:Th2 Cells / Q000276:immunology*
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D008565:Membrane Proteins; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; C585425:Tmem79 protein, mouse; C496349:Fgfr1 protein, mouse; D051496:Receptor, Fibroblast Growth Factor, Type 1
keywords: Allergic skin inflammation; Atopic dermatitis; Genetic lesions; Stat6; Th2 response