%0 Journal Article %J Nat Immunol %D 2004 %T Deletion of a conserved Il4 silencer impairs T helper type 1-mediated immunity. %A Ansel, K Mark %A Greenwald, Rebecca J %A Agarwal, Suneet %A Bassing, Craig H %A Monticelli, Silvia %A Interlandi, Jeneen %A Djuretic, Ivana M %A Lee, Dong U %A Sharpe, Arlene H %A Alt, Frederick W %A Rao, Anjana %K Animals %K Cell Differentiation %K Cells, Cultured %K Chromatin %K Conserved Sequence %K Cytokines %K Deoxyribonuclease I %K Gene Expression Regulation %K Gene Silencing %K Genetic Predisposition to Disease %K Interleukin-4 %K Leishmania major %K Leishmaniasis, Cutaneous %K Mice %K Mice, Knockout %K Regulatory Sequences, Nucleic Acid %K Sequence Deletion %K Th1 Cells %K Th2 Cells %X 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. %B Nat Immunol %V 5 %P 1251-9 %8 2004 Dec %G eng %N 12 %1 http://www.ncbi.nlm.nih.gov/pubmed/15516924?dopt=Abstract %R 10.1038/ni1135