The inflammasome adaptor ASC regulates adaptive immune cell functions by controlling DOCK2-mediated Rac activation and actin polymerization

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 cell...

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Autores principales: Ippagunta, Sirish K., Malireddi, R. K. Subbarao, Shaw, Patrick J., Neale, Geoffrey A., Vande Walle, Lieselotte, Green, Douglas R., Fukui, Yoshinori, Lamkanfi, Mohamed, Kanneganti, Thirumala-Devi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2011
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3178750/
https://www.ncbi.nlm.nih.gov/pubmed/21892172
http://dx.doi.org/10.1038/ni.2095
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author Ippagunta, Sirish K.
Malireddi, R. K. Subbarao
Shaw, Patrick J.
Neale, Geoffrey A.
Vande Walle, Lieselotte
Green, Douglas R.
Fukui, Yoshinori
Lamkanfi, Mohamed
Kanneganti, Thirumala-Devi
author_facet Ippagunta, Sirish K.
Malireddi, R. K. Subbarao
Shaw, Patrick J.
Neale, Geoffrey A.
Vande Walle, Lieselotte
Green, Douglas R.
Fukui, Yoshinori
Lamkanfi, Mohamed
Kanneganti, Thirumala-Devi
author_sort Ippagunta, Sirish K.
collection PubMed
description 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.
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spelling pubmed-31787502012-04-01 The inflammasome adaptor ASC regulates adaptive immune cell functions by controlling DOCK2-mediated Rac activation and actin polymerization Ippagunta, Sirish K. Malireddi, R. K. Subbarao Shaw, Patrick J. Neale, Geoffrey A. Vande Walle, Lieselotte Green, Douglas R. Fukui, Yoshinori Lamkanfi, Mohamed Kanneganti, Thirumala-Devi Nat Immunol Article 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. 2011-09-04 /pmc/articles/PMC3178750/ /pubmed/21892172 http://dx.doi.org/10.1038/ni.2095 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Ippagunta, Sirish K.
Malireddi, R. K. Subbarao
Shaw, Patrick J.
Neale, Geoffrey A.
Vande Walle, Lieselotte
Green, Douglas R.
Fukui, Yoshinori
Lamkanfi, Mohamed
Kanneganti, Thirumala-Devi
The inflammasome adaptor ASC regulates adaptive immune cell functions by controlling DOCK2-mediated Rac activation and actin polymerization
title The inflammasome adaptor ASC regulates adaptive immune cell functions by controlling DOCK2-mediated Rac activation and actin polymerization
title_full The inflammasome adaptor ASC regulates adaptive immune cell functions by controlling DOCK2-mediated Rac activation and actin polymerization
title_fullStr The inflammasome adaptor ASC regulates adaptive immune cell functions by controlling DOCK2-mediated Rac activation and actin polymerization
title_full_unstemmed The inflammasome adaptor ASC regulates adaptive immune cell functions by controlling DOCK2-mediated Rac activation and actin polymerization
title_short The inflammasome adaptor ASC regulates adaptive immune cell functions by controlling DOCK2-mediated Rac activation and actin polymerization
title_sort inflammasome adaptor asc regulates adaptive immune cell functions by controlling dock2-mediated rac activation and actin polymerization
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3178750/
https://www.ncbi.nlm.nih.gov/pubmed/21892172
http://dx.doi.org/10.1038/ni.2095
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