IgE hyperproduction through enhanced tyrosine phosphorylation of janus kinase 3 in NC/Nga mice, a model for human atopic dermatitis

Masahiro Matsumoto, Chisei Ra, Keiko Kawamoto, Hiroaki Sato, Atsuko Itakura, Junko Sawada, Hiroko Ushio, Hajime Suto, Kouichi Mitsuishi, Yoshiaki Hikasa, Hiroshi Matsuda

Research output: Contribution to journalArticlepeer-review

Abstract

IgE hyperproduction frequently observed in patients with atopic dermatitis (AD) may greatly contribute to the pathogenesis of AD, but its mechanisms are still unclear. NC/Nga mice raised in nonsterile circumstances spontaneously suffered from AD-like skin lesions with elevation of plasma IgE levels. We investigated mechanisms of the IgE hyperproduction in NC/Nga mice. Splenic T cells from SPF NC/Nga mice had a level of CD40 ligand (CD40L) expression comparable to that of BALB/c mice. Although there was no difference in the expression of CD40 on B cells between NC/Nga and BALB/c mice, B cells of NC/Nga mice produced much more IgE in the presence of soluble CD40L and IL-4. The stimulation with CD40L and/or IL-4 resulted in tyrosine phosphorylation of Janus kinase 3 (JAK3) in B cells, which was more strongly inducible in NC/Nga mice than in BALB/c mice. In B cells isolated from PBMC of AD patients with high serum IgE levels, JAK3 was constitutively phosphorylated at the tyrosine residue, and its phosphorylation was enhanced by the treatment with CD40L and/or IL-4 as was that in splenic B cells of NC/Nga mice with dermatitis and high IgE levels. Thus, it is suggested that constitutive and enhanced JAK3 phosphorylation in B cells highly sensitive to CD40L and IL-4 may be attributable to IgE hyperproduction in NC/Nga mice and patients with AD.

Original languageEnglish (US)
Pages (from-to)1056-1063
Number of pages8
JournalJournal of Immunology
Volume162
Issue number2
StatePublished - Jan 15 1999
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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