Deletion of a conserved Il4 silencer impairs T helper type 1–mediated immunity
- 31 October 2004
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Immunology
- Vol. 5 (12), 1251-1259
- https://doi.org/10.1038/ni1135
Abstract
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-γ also produced abundant interleukin 4 in vitro and in vivo. Despite mounting a vigorous interferon-γ 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.Keywords
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