An essential role for Rxrα in the development of Th2 responses

Xin Du, Koichi Tabeta, Navjiwan Mann, Karine Crozat, Suzanne Mudd, Bruce Beutler

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

A viable hypomorphic allele of mouse retinoid X receptor a (Rxra) was created by random germline mutagenesis. The mutation (I273N) alters the ligand binding and heterodimerization domain, and causes a 90% decline in ligand-inducible transactivation. Homozygotes develop progressive alopecia and dermal cysts, and progressive exaggeration of Th1 and loss of Th2 responses to antigen. Th1 skewing is directly caused by aberrant function of both antigen-presenting cells and naïve CD4 T cells; the predominant Th1 response to antigen is attributable to decreased suppression of regulatory T cells in mutant mouse. Dietary depletion of vitamin A in Th2-prone wildtype mice mimics the immune phenotype caused by the mutation. Hence, RXRα plays an important post-developmental role in the regulation of adaptive immune responses, and provides a plausible link between nutritional environment and the type of adaptive response that results from immunization.

Original languageEnglish (US)
Pages (from-to)3414-3423
Number of pages10
JournalEuropean Journal of Immunology
Volume35
Issue number12
DOIs
StatePublished - Dec 2005

Keywords

  • Allergy
  • Nuclear receptor
  • Retinoid X receptor α
  • Th1/Th2
  • Vitamin A

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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