IL-4 is a critical determinant in the generation of allergic inflammation initiated by a constitutively active Stat6.
IL-4 is required for the pathogenesis of atopic diseases and immune regulation. Stat6 is critical for IL-4-induced gene expression and Th cell differentiation. Recently, we have generated mice expressing a mutant Stat6 (Stat6VT) under control of the CD2 locus control region that is transcriptionally active independent of IL-4 stimulation. To determine whether active Stat6 in T cells is sufficient to alter immune regulation in vivo, we mated Stat6VT transgenic mice to IL-4-deficient mice. Stat6VT expression in IL-4-deficient lymphocytes was sufficient to alter lymphocyte homeostasis and promote Th2 differentiation in vitro. HyperTh2 levels in Stat6 transgenic mice correlated with an atopic phenotype that manifested as blepharitis and pulmonary inflammation with a high level of eosinophilic infiltration. In the absence of endogenous IL-4, Stat6VT transgenic mice were protected from allergic inflammation. Thus, in mice with hyperTh2 immune responses in vivo, IL-4 is a critical effector cytokine.
Sehra
Sarita
S
Department of Pediatrics, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Bruns
Heather A
HA
Ahyi
Ayele-Nati N
AN
Nguyen
Evelyn T
ET
Schmidt
Nathan W
NW
Michels
E Grace
EG
von Bülow
Götz-Ulrich
GU
Kaplan
Mark H
MH
D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D001762:Blepharitis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D050822:Cytokine Receptor gp130 / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D006706:Homeostasis / Q000235:genetics / Q000276:immunology; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology*; D015847:Interleukin-4 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D050800:STAT6 Transcription Factor / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology
C494199:IL6ST protein, human; D018836:Inflammation Mediators; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D050822:Cytokine Receptor gp130; D015847:Interleukin-4