Th2 LCR is essential for regulation of Th2 cytokine genes and for pathogenesis of allergic asthma

Byung Hee Koh, Soo Seok Hwang, Joo Young Kim, Wonyong Lee, Min Jong Kang, Chun Geun Lee, Jung Won Park, Richard A. Flavell, Gap Ryol Lee

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Previous studies have shown that Th2 cytokine genes on mouse chromosome 11 are coordinately regulated by the Th2 locus control region (LCR). To examine the in vivo function of Th2 LCR, we generated CD4-specific Th2 LCR-deficient (cLCR KO) mice using Cre-LoxP recombination. The number of CD4 T cells in the cLCR KO mouse was comparable to that in wild-type mice. The expression of Th2 cytokines was dramatically reduced in in vitro-stimulated naïve CD4 T cells. Deletion of the LCR led to a loss of general histone H3 acetylation and histone H3-K4 methylation, and demethylation of DNA in the Th2 cytokine locus. Upon ovalbumin challenge in the mouse model of allergic asthma, cLCR KO mice exhibited marked reduction in the recruitment of eosinophils and lymphocytes in the bronchoalveolar lavage fluid, serum IgE level, lung airway inflammation, mucus production in the airway walls, and airway hyperresponsiveness. These results directly demonstrate that the Th2 LCR is critically important in the regulation of Th2 cytokine genes, in chromatin remodeling of the Th2 cytokine locus, and in the pathogenesis of allergic asthma.

Original languageEnglish
Pages (from-to)10614-10619
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number23
DOIs
Publication statusPublished - 2010 Jun 8

All Science Journal Classification (ASJC) codes

  • General

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