Project description:This SuperSeries is composed of the following subset Series: GSE33596: Histone Deacetylase 3 is an Epigenomic Brake in Macrophage Alternative Activation (ChIP-Seq) GSE33608: Histone Deacetylase 3 is an Epigenomic Brake in Macrophage Alternative Activation (microarray) Refer to individual Series
Project description:Macrophages, a key cellular component of inflammation, become functionally polarized in a signal- and context-specific manner. Th2 cytokines such as 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. To determine if Histone Deacetylase 3 (HDAC3) has a role in macrophage polarization including alternative activation, we have performed global gene expression analysis in macrophages with and without HDAC3 and with or without IL-4 exposure. From this data, we conclude that macrophages lacking histone deacetylase 3 (HDAC3) display a polarization phenotype similar to IL-4 induced alternative activation and furthermore are hyper-responsive to IL-4 stimulation. Mouse bone marrow derived macrophages were obtained from both control and HDAC3 KO animals and treated with vehicle control (BSA) or IL-4 for 24 hours. RNA was isolated and subjected to analysis using an Agilent Whole Genome Microarray Kit.
Project description:Macrophages, a key cellular component of inflammation, become functionally polarized in a signal- and context-specific manner. Th2 cytokines such as 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. To determine if Histone Deacetylase 3 (HDAC3) has a role in macrophage polarization including alternative activation, we have performed global gene expression analysis in macrophages with and without HDAC3 and with or without IL-4 exposure. From this data, we conclude that macrophages lacking histone deacetylase 3 (HDAC3) display a polarization phenotype similar to IL-4 induced alternative activation and furthermore are hyper-responsive to IL-4 stimulation.
Project description:Effective host defense against infection relies on the tight coordination of immune activation, metabolic adaptation, and redox control, yet how these processes are integrated remains incompletely understood. Here, we identify dipeptidyl peptidase 3 (Dpp3) as a negative regulator of antimicrobial immunity. Dpp3-/- mice exhibit enhanced resistance to Klebsiella pneumoniae infection, with reduced bacterial burden, preserved tissue integrity, and attenuated systemic inflammation. This response is associated with increased phagocytic activity, expansion of germinal centres and plasma cells, and elevated interferon-γ production by T cells. Mechanistically, Dpp3 deficiency leads to reduced Nrf2 protein levels upon stimulation, resulting in heightened ROS accumulation and amplified NF-κB signaling. Integrated metabolomic and transcriptomic analyses of Dpp3-/- immune cells reveal mitochondrial dysfunction and a shift toward biosynthetic and antioxidant-supportive metabolic programs. Collectively, our findings identify Dpp3 as a molecular brake on host defense and uncover a regulatory axis linking redox balance, immunometabolism, and inflammation during infection.
