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

被引：97

作者：

Ippagunta, Sirish K. ^{[2
]}

Malireddi, R. K. Subbarao ^{[2
]}

Shaw, Patrick J. ^{[2
]}

Neale, Geoffrey A. ^{[3
]}

Vande Walle, Lieselotte ^{[1
,4
]}

Green, Douglas R. ^{[2
]}

Fukui, Yoshinori ^{[5
,6
]}

Lamkanfi, Mohamed ^{[1
,4
]}

Kanneganti, Thirumala-Devi ^{[2
]}

机构：

[1] Univ Ghent, Dept Biochem, B-9000 Ghent, Belgium

[2] St Jude Childrens Res Hosp, Dept Immunol, Memphis, TN 38105 USA

[3] St Jude Childrens Res Hosp, Dept Hartwell Ctr Bioinformat & Biotechnol, Memphis, TN 38105 USA

[4] VIB, Dept Med Prot Res, Ghent, Belgium

[5] Kyushu Univ, Div Immunogenet, Kyushu, Japan

[6] Kyushu Univ, Dept Immunobiol & Neurosci, Med Inst Bioregulat, Kyushu, Japan

来源：

NATURE IMMUNOLOGY | 2011年 / 12卷 / 10期

基金：

美国国家卫生研究院;

关键词：

SPECK-LIKE PROTEIN; HOST-DEFENSE; LISTERIA-MONOCYTOGENES; CASPASE-1; ACTIVATION; AIM2; INFLAMMASOME; INDUCED ARTHRITIS; INDEPENDENT ROLE; VIRAL-INFECTION; CARD ASC; IPAF;

D O I：

10.1038/ni.2095

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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 cytoplasmic receptor NLRP3 or caspase-1, controlled the mRNA stability and expression of Dock2, a guanine nucleotide-exchange factor that mediates Rac-dependent signaling in cells of the immune response. Dock2-deficient DCs showed defective antigen uptake similar to that of ASC-deficient 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 actin polymerization in DCs and lymphocytes.

引用

页码：1010 / U122

页数：9

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