IL-4 is a critical determinant in the generation of allergic inflammation initiated by a constitutively active Stat6

Sarita Sehra, Heather A. Bruns, Ayele Nati N Ahyi, Evelyn T. Nguyen, Nathan W. Schmidt, E. Grace Michels, Götz Ulrich Von Bülow, Mark Kaplan

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)3551-3559
Number of pages9
JournalJournal of Immunology
Volume180
Issue number5
StatePublished - Mar 1 2008

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Interleukin-4
Inflammation
Transgenic Mice
Locus Control Region
Blepharitis
Lymphocytes
Immune System Diseases
Cell Differentiation
Pneumonia
Homeostasis
Cytokines
T-Lymphocytes
Phenotype
Gene Expression

ASJC Scopus subject areas

  • Immunology

Cite this

Sehra, S., Bruns, H. A., Ahyi, A. N. N., Nguyen, E. T., Schmidt, N. W., Michels, E. G., ... Kaplan, M. (2008). IL-4 is a critical determinant in the generation of allergic inflammation initiated by a constitutively active Stat6. Journal of Immunology, 180(5), 3551-3559.

IL-4 is a critical determinant in the generation of allergic inflammation initiated by a constitutively active Stat6. / Sehra, Sarita; Bruns, Heather A.; Ahyi, Ayele Nati N; Nguyen, Evelyn T.; Schmidt, Nathan W.; Michels, E. Grace; Von Bülow, Götz Ulrich; Kaplan, Mark.

In: Journal of Immunology, Vol. 180, No. 5, 01.03.2008, p. 3551-3559.

Research output: Contribution to journalArticle

Sehra, S, Bruns, HA, Ahyi, ANN, Nguyen, ET, Schmidt, NW, Michels, EG, Von Bülow, GU & Kaplan, M 2008, 'IL-4 is a critical determinant in the generation of allergic inflammation initiated by a constitutively active Stat6', Journal of Immunology, vol. 180, no. 5, pp. 3551-3559.
Sehra S, Bruns HA, Ahyi ANN, Nguyen ET, Schmidt NW, Michels EG et al. IL-4 is a critical determinant in the generation of allergic inflammation initiated by a constitutively active Stat6. Journal of Immunology. 2008 Mar 1;180(5):3551-3559.
Sehra, Sarita ; Bruns, Heather A. ; Ahyi, Ayele Nati N ; Nguyen, Evelyn T. ; Schmidt, Nathan W. ; Michels, E. Grace ; Von Bülow, Götz Ulrich ; Kaplan, Mark. / IL-4 is a critical determinant in the generation of allergic inflammation initiated by a constitutively active Stat6. In: Journal of Immunology. 2008 ; Vol. 180, No. 5. pp. 3551-3559.
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