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Publication : Deletion of a conserved Il4 silencer impairs T helper type 1-mediated immunity.

First Author  Ansel KM Year  2004
Journal  Nat Immunol Volume  5
Issue  12 Pages  1251-9
PubMed ID  15516924 Mgi Jnum  J:94039
Mgi Id  MGI:3510564 Doi  10.1038/ni1135
Citation  Ansel KM, et al. (2004) Deletion of a conserved Il4 silencer impairs T helper type 1-mediated immunity. Nat Immunol 5(12):1251-9
abstractText  Helper T cell differentiation involves silencing as well as activation of gene expression. We have identified a conserved silencer of the gene encoding interleukin 4 (Il4) marked by DNase I hypersensitivity (HS IV) and permissive chromatin structure in all helper T cells. Deletion of HS IV increased Il4 and Il13 transcription by naive T cells and led to T helper type 2 skewing in vitro. HS IV controlled Il4 silencing during T helper type 1 differentiation, as HS IV-deficient T helper type 1 cells that expressed interferon-gamma also produced abundant interleukin 4 in vitro and in vivo. Despite mounting a vigorous interferon-gamma response, HS IV-deficient mice were more susceptible to Leishmania major infection than were wild-type littermate control mice, showing a critical function for Il4 silencing in T helper type 1-mediated immunity.
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