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PMID: 20483988 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 107 ·No. 23 ·2010-06-08 ·Pages 10614-9

Koh BH, Hwang SS, Kim JY, Lee W, Kang MJ, Lee CG, Park JW, Flavell RA, Lee GR

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.

MeSH Terms
Animals Asthma/etiology,genetics,immunology,pathology Cell Lineage Cytokines/genetics,immunology Gene Expression Regulation Hypersensitivity/complications,immunology Immunity, Innate Locus Control Region Mice Mice, Knockout Th2 Cells/immunology,metabolism
Chemicals
Cytokines
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Koh Byung Hee
Department of Life Science, Sogang University, Seoul 121-742, Korea.
Hwang Soo Seok
Kim Joo Young
Lee Wonyong
Kang Min-Jong
Lee Chun Geun
Park Jung-Won
Flavell Richard A
Lee Gap Ryol
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.1005383107
Published
2010-06-08
Epub
2010-00-18
Pages
10614-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC2890814
Subset
IM
Grants
NHLBI NIH HHS · P01 HL056389 · United States
NHLBI NIH HHS · P50 HL056389 · United States
NHLBI NIH HHS · HL56389 · United States
Howard Hughes Medical Institute · United States
External Links
PubMed source DOI: 10.1073/pnas.1005383107 PMC Full Text View journal details
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