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PMID: 20177071 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Inflammasome-independent role of apoptosis-associated speck-like protein containing a CARD (ASC) in T cell priming is critical for collagen-induced arthritis.

The Journal of biological chemistry ·Vol. 285 ·No. 16 ·2010-04-16 ·Pages 12454-62

Ippagunta SK, Brand DD, Luo J, Boyd KL, Calabrese C, Stienstra R, Van de Veerdonk FL, Netea MG, Joosten LA, Lamkanfi M, Kanneganti TD

Abstract

Rheumatoid arthritis is an autoimmune disease with 1% prevalence in the industrialized world. The contributions of the inflammasome components Nlrp3, ASC, and caspase-1 in the pathogenesis of collagen-induced arthritis have not been characterized. Here, we show that ASC(-/-) mice were protected from arthritis, whereas Nlrp3(-/-) and caspase-1(-/-) mice were susceptible to collagen-induced arthritis. Unlike Nlrp3(-/-) and caspase-1(-/-) mice, the production of collagen-specific antibodies was abolished in ASC(-/-) mice. This was due to a significantly reduced antigen-specific activation of lymphocytes by ASC(-/-) dendritic cells. Antigen-induced proliferation of purified ASC(-/-) T cells was restored upon incubation with wild type dendritic cells, but not when cultured with ASC(-/-) dendritic cells. Moreover, direct T cell receptor ligation with CD3 and CD28 antibodies induced a potent proliferation of ASC(-/-) T cells, indicating that ASC is specifically required in dendritic cells for antigen-induced T cell activation. Therefore, ASC fulfills a hitherto unrecognized inflammasome-independent role in dendritic cells that is crucial for T cell priming and the induction of antigen-specific cellular and humoral immunity and the onset of collagen-induced arthritis.

MeSH Terms
Animals Apoptosis Regulatory Proteins Arthritis, Experimental/etiology,immunology,pathology Autoantibodies/biosynthesis CARD Signaling Adaptor Proteins Carrier Proteins/genetics,immunology Caspase 1/deficiency,genetics,immunology Collagen/immunology Cytoskeletal Proteins/deficiency,genetics,immunology Dendritic Cells/immunology Humans Lymphocyte Activation Mice Mice, Inbred C57BL Mice, Knockout NLR Family, Pyrin Domain-Containing 3 Protein T-Lymphocytes/immunology
Chemicals
Apoptosis Regulatory Proteins Autoantibodies CARD Signaling Adaptor Proteins Carrier Proteins Cytoskeletal Proteins NLR Family, Pyrin Domain-Containing 3 Protein Nlrp3 protein, mouse Pycard protein, mouse Collagen Caspase 1
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Ippagunta Sirish K
Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Brand David D
Luo Jiwen
Boyd Kelli L
Calabrese Christopher
Stienstra Rinke
Van de Veerdonk Frank L
Netea Mihai G
Joosten Leo A B
Lamkanfi Mohamed
Kanneganti Thirumala-Devi
References (25)
25 references, click to expand
  1. Converting enzyme-independent release of tumor necrosis factor alpha and IL-1beta from a stimulated human monocytic cell line in the presence of activated neutrophils or purified proteinase 3.
    Proc Natl Acad Sci U S A. 1999 May 25;96(11):6261-6 PMID: 10339575
  2. T-cell receptor V beta genes repertoire in mice. Possible role in resistance and susceptibility to type II collagen-induced arthritis.
    J Autoimmun. 1990 Apr;3(2):113-21 PMID: 2140260
  3. The inflammasomes: guardians of the body.
    Annu Rev Immunol. 2009;27:229-65 PMID: 19302040
  4. Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3.
    Nature. 2006 Mar 9;440(7081):233-6 PMID: 16407888
  5. Immunisation against heterologous type II collagen induces arthritis in mice.
    Nature. 1980 Feb 14;283(5748):666-8 PMID: 6153460
  6. Type II collagen autoimmunity in animals and provocations leading to arthritis.
    Immunol Rev. 1990 Dec;118:193-232 PMID: 2079326
  7. Dipeptidyl peptidase I activates neutrophil-derived serine proteases and regulates the development of acute experimental arthritis.
    J Clin Invest. 2002 Feb;109(3):363-71 PMID: 11827996
  8. The intracellular sensor NLRP3 mediates key innate and healing responses to influenza A virus via the regulation of caspase-1.
    Immunity. 2009 Apr 17;30(4):566-75 PMID: 19362023
  9. Autoimmune recognition of cartilage collagens.
    Ann Med. 1993 Jun;25(3):251-64 PMID: 8333924
  10. Molecular mechanisms involved in inflammasome activation.
    Trends Cell Biol. 2009 Sep;19(9):455-64 PMID: 19716304
  11. Granzyme A is an interleukin 1 beta-converting enzyme.
    J Exp Med. 1995 May 1;181(5):1917-22 PMID: 7722467
  12. The NLR gene family: a standard nomenclature.
    Immunity. 2008 Mar;28(3):285-7 PMID: 18341998
  13. NLRs at the intersection of cell death and immunity.
    Nat Rev Immunol. 2008 May;8(5):372-9 PMID: 18362948
  14. Intracellular NOD-like receptors in host defense and disease.
    Immunity. 2007 Oct;27(4):549-59 PMID: 17967410
  15. Inflammatory role of ASC in antigen-induced arthritis is independent of caspase-1, NALP-3, and IPAF.
    J Immunol. 2009 Sep 15;183(6):4003-12 PMID: 19717512
  16. NALP3: a key player in caspase-1 activation.
    J Endotoxin Res. 2006;12(4):251-6 PMID: 16953978
  17. Isolation and characterization of a collagen from chick cartilage containing three identical alpha chains.
    Biochemistry. 1971 Apr 27;10(9):1652-9 PMID: 4325605
  18. (S)-1-((S)-2-{[1-(4-amino-3-chloro-phenyl)-methanoyl]-amino}-3,3-dimethyl-butanoyl)-pyrrolidine-2-carboxylic acid ((2R,3S)-2-ethoxy-5-oxo-tetrahydro-furan-3-yl)-amide (VX-765), an orally available selective interleukin (IL)-converting enzyme/caspase-1 inhibitor, exhibits potent anti-inflammatory activities by inhibiting the release of IL-1beta and IL-18.
    J Pharmacol Exp Ther. 2007 May;321(2):509-16 PMID: 17289835
  19. Collagen-induced arthritis.
    Nat Protoc. 2007;2(5):1269-75 PMID: 17546023
  20. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta.
    Mol Cell. 2002 Aug;10(2):417-26 PMID: 12191486
  21. Autoimmunity to type II collagen an experimental model of arthritis.
    J Exp Med. 1977 Sep 1;146(3):857-68 PMID: 894190
  22. Prevention of cold-associated acute inflammation in familial cold autoinflammatory syndrome by interleukin-1 receptor antagonist.
    Lancet. 2004 Nov 13-19;364(9447):1779-85 PMID: 15541451
  23. Stimulation of Toll-like receptor 3 and 4 induces interleukin-1beta maturation by caspase-8.
    J Exp Med. 2008 Sep 1;205(9):1967-73 PMID: 18725521
  24. Fungal zymosan and mannan activate the cryopyrin inflammasome.
    J Biol Chem. 2009 Jul 31;284(31):20574-81 PMID: 19509280
  25. Inflammasomes: guardians of cytosolic sanctity.
    Immunol Rev. 2009 Jan;227(1):95-105 PMID: 19120479
Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
1083-351X
DOI
10.1074/jbc.M109.093252
Published
2010-04-16
Epub
2010-00-22
Pages
12454-62
Language
English
Region
United States
NLM ID
2985121R
PMCID
PMC2852983
Subset
IM
Grants
NIAMS NIH HHS · R01 AR056296 · United States
NIAMS NIH HHS · AR056296 · United States
External Links
PubMed source DOI: 10.1074/jbc.M109.093252 PMC Full Text View journal details
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