HDAC3deltaIEC
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Theresa Alenghat
PROVIDER: E-GEOD-50190 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Publications
Histone deacetylase 3 coordinates commensal-bacteria-dependent intestinal homeostasis.
Alenghat Theresa T Osborne Lisa C LC Saenz Steven A SA Kobuley Dmytro D Ziegler Carly G K CG Mullican Shannon E SE Choi Inchan I Grunberg Stephanie S Sinha Rohini R Wynosky-Dolfi Meghan M Snyder Annelise A Giacomin Paul R PR Joyce Karen L KL Hoang Tram B TB Bewtra Meenakshi M Brodsky Igor E IE Sonnenberg Gregory F GF Bushman Frederic D FD Won Kyoung-Jae KJ Lazar Mitchell A MA Artis David D
Nature 20131103 7478
The development and severity of inflammatory bowel diseases and other chronic inflammatory conditions can be influenced by host genetic and environmental factors, including signals derived from commensal bacteria. However, the mechanisms that integrate these diverse cues remain undefined. Here we demonstrate that mice with an intestinal epithelial cell (IEC)-specific deletion of the epigenome-modifying enzyme histone deacetylase 3 (HDAC3(ΔIEC) mice) exhibited extensive dysregulation of IEC-intri ...[more]
Similar Datasets
Project description:Innate lymphoid cells (ILCs) are a recently recognized heterogenous group of immune cells that are critical in orchestrating immunity and inflammation in the intestine, but whether ILCs influence immune responses or tissue homeostasis at other mucosal sites remains poorly characterized. Here we identify a population of lung-resident ILCs in mice and humans that expressed the alloantigen Thy-1 (CD90), interleukin 2 (IL-2) receptor a-chain (CD25), IL-7 receptor a-chain (CD127) and the IL-33 receptor subunit T1-ST2. Notably, mouse ILCs accumulated in the lung after infection with influenza virus, and depletion of ILCs resulted in loss of airway epithelial integrity, diminished lung function and impaired airway remodeling. These defects were restored by administration of the lung ILC product amphiregulin. Collectively, our results demonstrate a critical role for lung ILCs in restoring airway epithelial integrity and tissue homeostasis after infection with influenza virus. As part of this study, we performed gene expression profiling to examine how the transcriptional signatures compared between murine naïve group 2 lung ILC and group 3 splenic LTi cell populations. Group 2 ILCs from the lung (Lin- CD90+ CD25+ T1/ST2+) and Group 3 LTi cells from the spleen (Lin- CD90+ CD25+ CD4+) were sort-purified from naive wildtype C57BL/6 mice using BD FACS Aria. Four biological replicates were collected, each replicate containing 1.5 x 104 to 2 x104 cells sorted to a purity >97% from six pooled lungs (ILCs) or 10 pooled spleens (LTi cells). Cells were sorted directly into TRIzol LS (Invitrogen), then mRNA was isolated, amplified, labeled, and hybridized to Affymetrix GeneChip (Mouse Gene 1.0 ST).
2013-04-30 | E-GEOD-46468 | biostudies-arrayexpress
Project description:The development and severity of inflammatory bowel diseases (IBD) and other chronic inflammatory conditions can be influenced by host genetic and environmental factors, including signals derived from commensal bacteria. However, the mechanisms that integrate these diverse cues remain undefined. Here we demonstrate that intestinal epithelial cells (IECs) isolated from IBD patients exhibit decreased expression of the epigenome-modifying enzyme histone deacetylase 3 (HDAC3). Further, genome-wide analyses of murine IECs that lack HDAC3 (HDAC3ΔIEC) revealed that HDAC3 deficiency resulted in dysregulated gene expression coupled with alterations in histone acetylation. Critically, conventionally-housed HDAC3ΔIEC mice demonstrated loss of Paneth cells, impaired IEC function and alterations in the composition of intestinal commensal bacteria. In addition, HDAC3ΔIEC mice exhibited significantly increased susceptibility to intestinal damage and inflammation, indicating that epithelial expression of HDAC3 plays a central role in maintaining intestinal homeostasis. Strikingly, rederivation of HDAC3ΔIEC mice into germ-free conditions revealed that dysregulated IEC gene expression, Paneth cell homeostasis, and intestinal barrier function were largely restored in the absence of commensal bacteria. Collectively, these data indicate that the HDAC3 is a critical factor that integrates commensal bacteria-derived signals to calibrate epithelial cell responses required to establish normal host-commensal relationships and maintain intestinal homeostasis. In this study, we performed gene expression profiling to examine how the transcriptional profiles in primary live, EpCAM+ IECs from the large intestine differed between germ-free control HDAC3FF mice (3 biological replicates) and germ-free IEC-intrinsic knockout HDAC3ΔIEC mice (3 biological replicates).
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Project description:The development and severity of inflammatory bowel diseases (IBD) and other chronic inflammatory conditions can be influenced by host genetic and environmental factors, including signals derived from commensal bacteria. However, the mechanisms that integrate these diverse cues remain undefined. Here we demonstrate that intestinal epithelial cells (IECs) isolated from IBD patients exhibit decreased expression of the epigenome-modifying enzyme histone deacetylase 3 (HDAC3). Further, genome-wide analyses of murine IECs that lack HDAC3 (HDAC3?IEC) revealed that HDAC3 deficiency resulted in dysregulated gene expression coupled with alterations in histone acetylation. Critically, conventionally-housed HDAC3?IEC mice demonstrated loss of Paneth cells, impaired IEC function and alterations in the composition of intestinal commensal bacteria. In addition, HDAC3?IEC mice exhibited significantly increased susceptibility to intestinal damage and inflammation, indicating that epithelial expression of HDAC3 plays a central role in maintaining intestinal homeostasis. Strikingly, rederivation of HDAC3?IEC mice into germ-free conditions revealed that dysregulated IEC gene expression, Paneth cell homeostasis, and intestinal barrier function were largely restored in the absence of commensal bacteria. Collectively, these data indicate that the HDAC3 is a critical factor that integrates commensal bacteria-derived signals to calibrate epithelial cell responses required to establish normal host-commensal relationships and maintain intestinal homeostasis. In this study, we performed gene expression profiling to examine how the transcriptional profiles in primary live, EpCAM+ IECs from the large intestine differed between control HDAC3FF mice (3 biological replicates) and IEC-intrinsic knockout HDAC3?IEC mice (3 biological replicates).
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