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

Sirish K. Ippagunta, David Brand, Jiwen Luo, Kelli L. Boyd, Christopher Calabrese, Rinke Stienstra, Frank L. Van De Veerdonk, Mihai G. Netea, Leo A.B. Joosten, Mohamed Lamkanfi, Thirumala Devi Kanneganti

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)12454-12462
Number of pages9
JournalJournal of Biological Chemistry
Volume285
Issue number16
DOIs
StatePublished - Apr 16 2010

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Inflammasomes
Experimental Arthritis
T-cells
Dendritic Cells
Collagen
Caspase 1
Apoptosis
T-Lymphocytes
Antigens
Proteins
Chemical activation
CD27 Antigens
Lymphocytes
Antibodies
Lymphocyte Activation
Humoral Immunity
T-Cell Antigen Receptor
Cellular Immunity
Autoimmune Diseases
Arthritis

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Inflammasome-independent role of apoptosis-associated speck-like protein containing a CARD (ASC) in T cell priming is critical for collagen-induced arthritis. / Ippagunta, Sirish K.; Brand, David; 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.

In: Journal of Biological Chemistry, Vol. 285, No. 16, 16.04.2010, p. 12454-12462.

Research output: Contribution to journalArticle

Ippagunta, SK, Brand, D, Luo, J, Boyd, KL, Calabrese, C, Stienstra, R, Van De Veerdonk, FL, Netea, MG, Joosten, LAB, Lamkanfi, M & Kanneganti, TD 2010, 'Inflammasome-independent role of apoptosis-associated speck-like protein containing a CARD (ASC) in T cell priming is critical for collagen-induced arthritis', Journal of Biological Chemistry, vol. 285, no. 16, pp. 12454-12462. https://doi.org/10.1074/jbc.M109.093252
Ippagunta, Sirish K. ; Brand, David ; 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. / Inflammasome-independent role of apoptosis-associated speck-like protein containing a CARD (ASC) in T cell priming is critical for collagen-induced arthritis. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 16. pp. 12454-12462.
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