| First Author | Mullican SE | Year | 2011 |
| Journal | Genes Dev | Volume | 25 |
| Issue | 23 | Pages | 2480-8 |
| PubMed ID | 22156208 | Mgi Jnum | J:178911 |
| Mgi Id | MGI:5300624 | Doi | 10.1101/gad.175950.111 |
| Citation | Mullican SE, et al. (2011) Histone deacetylase 3 is an epigenomic brake in macrophage alternative activation. Genes Dev 25(23):2480-8 |
| abstractText | Macrophages, a key cellular component of inflammation, become functionally polarized in a signal- and context-specific manner. Th2 cytokines such as interleukin 4 (IL-4) polarize macrophages to a state of alternative activation that limits inflammation and promotes wound healing. Alternative activation is mediated by a transcriptional program that is influenced by epigenomic modifications, including histone acetylation. Here we report that macrophages lacking histone deacetylase 3 (HDAC3) display a polarization phenotype similar to IL-4-induced alternative activation and, furthermore, are hyperresponsive to IL-4 stimulation. Throughout the macrophage genome, HDAC3 deacetylates histone tails at regulatory regions, leading to repression of many IL-4-regulated genes characteristic of alternative activation. Following exposure to Schistosoma mansoni eggs, a model of Th2 cytokine-mediated disease that is limited by alternative activation, pulmonary inflammation was ameliorated in mice lacking HDAC3 in macrophages. Thus, HDAC3 functions in alternative activation as a brake whose release could be of benefit in the treatment of multiple inflammatory diseases. |
