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

Sirish K. Ippagunta, R. K.Subbarao Malireddi, Patrick J. Shaw, Geoffrey A. Neale, Lieselotte Vande Walle, Douglas R. Green, Yoshinori Fukui, Mohamed Lamkanfi, Thirumala Devi Kanneganti

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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 nucleotideĝ€"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.

Original languageEnglish
Pages (from-to)1010-1016
Number of pages7
JournalNature Immunology
Volume12
Issue number10
DOIs
Publication statusPublished - Oct 1 2011

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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    Ippagunta, S. K., Malireddi, R. K. S., Shaw, P. J., Neale, G. A., Walle, L. V., Green, D. R., Fukui, Y., Lamkanfi, M., & Kanneganti, T. D. (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), 1010-1016. https://doi.org/10.1038/ni.2095