Transcriptomics

Dataset Information

66

Comparison of gene expression profiles in naïve WT and Asc-null bone marrow derived dendritic cells


ABSTRACT: The adaptor protein ASC contributes to innate immunity through the assembly of caspase-1-activating inflammasome complexes. We demonstrate that ASC plays an inflammasome-independent cell-intrinsic role in adaptive immune cells. Asc-/- mice displayed defective antigen presentation by dendritic cells and lymphocyte migration due to impaired Rac-mediated actin polymerization. Genome-wide analysis showed that ASC, but not Nlrp3 or caspase-1, controls mRNA stability and expression of DOCK2, a guanine nucleotide exchange factor that mediates Rac-dependent signaling in immune cells. DOCK2-deficient dendritic cells showed similar defective antigen uptake as Asc-/- cells. Ectopic expression of DOCK2 in ASC-deficient cells restored Rac-mediated actin polymerization, antigen uptake and chemotaxis. Thus, ASC shapes adaptive immunity independently of inflammasomes by modulating DOCK2-dependent Rac activation and F-actin polymerization in dendritic cells and lymphocytes. Three replicates of naïve WT and three replicates of Asc-/- bone marrow derived dendritic cells were analyzed on the Affymetrix HT MG-430 PM plate array.

ORGANISM(S): Mus musculus  

SUBMITTER: R K Malireddi   Sirish K Ippagunta  Patrick J Shaw  Thirumala-Devi Kanneganti  Geoffrey Neale  Geoffrey A Neale 

PROVIDER: E-GEOD-30769 | ArrayExpress | 2012-07-08

SECONDARY ACCESSION(S): GSE30769PRJNA144331

REPOSITORIES: GEO, ArrayExpress

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Publications

The inflammasome adaptor ASC regulates the function of adaptive immune cells by controlling Dock2-mediated Rac activation and actin polymerization.

Ippagunta Sirish K SK   Malireddi R K Subbarao RK   Shaw Patrick J PJ   Neale Geoffrey A GA   Vande Walle Lieselotte L   Green Douglas R DR   Fukui Yoshinori Y   Lamkanfi Mohamed M   Kanneganti Thirumala-Devi TD  

Nature immunology 20110904 10


The adaptor ASC contributes to innate immunity through the assembly of inflammasome complexes that activate the cysteine protease caspase-1. Here we demonstrate that ASC has an inflammasome-independent, cell-intrinsic role in cells of the adaptive immune response. ASC-deficient mice showed defective antigen presentation by dendritic cells (DCs) and lymphocyte migration due to impaired actin polymerization mediated by the small GTPase Rac. Genome-wide analysis showed that ASC, but not the cytopla  ...[more]

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