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

Nature Immunology volume 12, pages 10101016 (2011) | Download Citation

  • An Addendum to this article was published on 19 June 2012

This article has been updated


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.

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  • 01 June 2012

    In the version of this article initially published, the authors identified a defect in Dock2 expression in ASC-deficient (Pycard/) mice that was not related to the inflammasome. With this addendum statement and figure, the authors now report that not all ACS-deficient strains have this defect, to alert the community to this finding.


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We thank R. Flavell (Yale University School of Medicine), G. Nunez (University of Michigan) and S. Akira (Osaka University) for mutant mice; P. Vandenabeele (Ghent University) for anti-caspase-1; and H. Chi (St. Jude Children's Research Hospital) for retroviral plasmids and mutant mice. Supported by the US National Institutes of Health (R01AR056296 and R21AI088177 to T.-D.K.), the American Lebanese Syrian Associated Charities (T.-D.K.), the European Union Framework Program 7 (Marie-Curie grant 256432 to M.L.) and the Fund for Scientific Research-Flanders (M.L. and L.V.W.).

Author information

Author notes

    • Sirish K Ippagunta
    • , R K Subbarao Malireddi
    •  & Patrick J Shaw

    These authors contributed equally to this work.


  1. Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

    • Sirish K Ippagunta
    • , R K Subbarao Malireddi
    • , Patrick J Shaw
    • , Douglas R Green
    •  & Thirumala-Devi Kanneganti
  2. Department of Hartwell Center for Bioinformatics & Biotechnology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

    • Geoffrey A Neale
  3. Department of Biochemistry, Ghent University, Ghent, Belgium.

    • Lieselotte Vande Walle
    •  & Mohamed Lamkanfi
  4. Department of Medical Protein Research, VIB, Ghent, Belgium.

    • Lieselotte Vande Walle
    •  & Mohamed Lamkanfi
  5. Division of Immunogenetics, Kyushu University, Kyushu, Japan.

    • Yoshinori Fukui
  6. Department of Immunobiology and Neuroscience Medical Institute of Bioregulation, Kyushu University, Kyushu, Japan.

    • Yoshinori Fukui


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T.-D.K., M.L., S.K.I., P.J.S. and R.K.S.M. designed research; S.K.I., P.J.S., R.K.S.M., did research; G.A.N. did bioinformatic analyses; L.V.W. confirmed ASC-dependent Dock2 expression in an independently generated line of ASC-deficient mice; D.R.G. contributed to the writing of the manuscript and conceptual insights; Y.F. provided reagents; T.-D.K., M.L., S.K.I., P.J.S., R.K.S.M., G.A.N. and Y.F. analyzed data; P.J.S., M.L. and T.-D.K. wrote the paper; and T.-D.K. conceived of the study, designed the experiments and provided overall direction.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Mohamed Lamkanfi or Thirumala-Devi Kanneganti.

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