IL-4 regulates skin homeostasis and the predisposition toward allergic skin inflammation.
IL-4 promotes the development of Th2 cells and allergic inflammation. In atopic dermatitis lesions, IL-4 decreases the expression of multiple genes associated with innate defense, including genes in the epidermal differentiation complex (EDC) that regulate epidermal barrier function. However, it is not clear whether IL-4 also contributes to homeostatic control of EDC genes. In this report, we demonstrate that expression of EDC genes and barrier function is increased in the absence of endogenous IL-4. Mice that express a constitutively active Stat6 (Stat6VT) are prone to the development of allergic skin inflammation and have decreased expression of EDC genes. IL-4 deficiency protects Stat6VT transgenic mice from the development of allergic skin inflammation and decreased recovery time in barrier function following skin irritation, with a concomitant increase in EDC gene expression. These data suggest that IL-4 plays an important role in regulating epidermal homeostasis and innate barrier function.
Sehra
Sarita
S
Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Yao
Yongxue
Y
Howell
Michael D
MD
Nguyen
Evelyn T
ET
Kansas
Geoffrey S
GS
Leung
Donald Y M
DY
Travers
Jeffrey B
JB
Kaplan
Mark H
MH
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D003876:Dermatitis, Atopic / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D004817:Epidermis / Q000276:immunology / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D020022:Genetic Predisposition to Disease; D006706:Homeostasis / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D018836:Inflammation Mediators / Q000502:physiology*; D015847:Interleukin-4 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010539:Permeability; D050800:STAT6 Transcription Factor / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D018836:Inflammation Mediators; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015847:Interleukin-4