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

(2011) NATURE IMMUNOLOGY. 12(10). p.1010-U122
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Abstract
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.
Keywords
CARD ASC, VIRAL-INFECTION, INDEPENDENT ROLE, IPAF, INDUCED ARTHRITIS, AIM2 INFLAMMASOME, CASPASE-1 ACTIVATION, LISTERIA-MONOCYTOGENES, HOST-DEFENSE, SPECK-LIKE PROTEIN

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Chicago
Ippagunta, Sirish K, RK Subbarao Malireddi, Patrick J Shaw, Geoffrey A Neale, Lieselotte Vande Walle, Douglas R Green, Yoshinori Fukui, Mohamed Lamkanfi, and Thirumala-Devi Kanneganti. 2011. “The Inflammasome Adaptor ASC Regulates the Function of Adaptive Immune Cells by Controlling Dock2-mediated Rac Activation and Actin Polymerization.” Nature Immunology 12 (10): 1010–U122.
APA
Ippagunta, S. K., Malireddi, R. S., Shaw, P. J., Neale, G. A., Vande Walle, L., Green, D. R., Fukui, Y., et al. (2011). The inflammasome adaptor ASC regulates the function of adaptive immune cells by controlling Dock2-mediated Rac activation and actin polymerization. NATURE IMMUNOLOGY, 12(10), 1010–U122.
Vancouver
1.
Ippagunta SK, Malireddi RS, Shaw PJ, Neale GA, Vande Walle L, Green DR, et al. The inflammasome adaptor ASC regulates the function of adaptive immune cells by controlling Dock2-mediated Rac activation and actin polymerization. NATURE IMMUNOLOGY. 2011;12(10):1010–U122.
MLA
Ippagunta, Sirish K, RK Subbarao Malireddi, Patrick J Shaw, et al. “The Inflammasome Adaptor ASC Regulates the Function of Adaptive Immune Cells by Controlling Dock2-mediated Rac Activation and Actin Polymerization.” NATURE IMMUNOLOGY 12.10 (2011): 1010–U122. Print.
@article{1956163,
  abstract     = {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.},
  author       = {Ippagunta, Sirish K and Malireddi, RK Subbarao and Shaw, Patrick J and Neale, Geoffrey A and Vande Walle, Lieselotte and Green, Douglas R and Fukui, Yoshinori and Lamkanfi, Mohamed and Kanneganti, Thirumala-Devi},
  issn         = {1529-2908},
  journal      = {NATURE IMMUNOLOGY},
  keyword      = {CARD ASC,VIRAL-INFECTION,INDEPENDENT ROLE,IPAF,INDUCED ARTHRITIS,AIM2 INFLAMMASOME,CASPASE-1 ACTIVATION,LISTERIA-MONOCYTOGENES,HOST-DEFENSE,SPECK-LIKE PROTEIN},
  language     = {eng},
  number       = {10},
  pages        = {1010--U122},
  title        = {The inflammasome adaptor ASC regulates the function of adaptive immune cells by controlling Dock2-mediated Rac activation and actin polymerization},
  url          = {http://dx.doi.org/10.1038/ni.2095},
  volume       = {12},
  year         = {2011},
}

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