Impaired cytokine signaling in mice lacking the IL-1 receptor- associated kinase

James A. Thomas, Jerry L. Allen, May Tsen, Todd Dubnicoff, Jay Danao, X. Charlene Liao, Zhaodan Cao, Steven A. Wasserman

Research output: Contribution to journalArticle

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Abstract

Stimulation of the type 1 IL-1R (IL-1R1) and the IL-18R by their cognate ligands induces recruitment of the IL-1R-associated kinase (IRAK). Activation of IRAK leads in turn to nuclear translocation of NF-κB, which directs expression of innate and adaptive immune response genes. To study IRAK function in cytokine signaling, we generated cells and mice lacking the IRAK protein. IRAK-deficient fibroblasts show diminished activation of NF-κB when stimulated with IL- 1. Immune effector cells without IRAK exhibit a defective IFN-γ response to costimulation with IL-18. Furthermore, mice lacking the Irak gene demonstrate an attenuated response to injected IL-1. Deletion of Irak, however, does not affect the ability of mice to develop delayed-type hypersensitivity or clear infection with the intracellular parasite, Listeria monocytogenes. These results demonstrate that although IRAK participates in IL-1 and IL-18 signal transduction, residual cytokine responsiveness operates through an IRAK-independent pathway.

Original languageEnglish (US)
Pages (from-to)978-984
Number of pages7
JournalJournal of Immunology
Volume163
Issue number2
StatePublished - Jul 15 1999

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Interleukin-1 Receptor-Associated Kinases
Phosphotransferases
Cytokines
Interleukin-1
Interleukin-18
Delayed Hypersensitivity
Listeria monocytogenes
Adaptive Immunity
Innate Immunity
Protein Kinases
Genes
Signal Transduction
Parasites
Fibroblasts
Ligands

ASJC Scopus subject areas

  • Immunology

Cite this

Thomas, J. A., Allen, J. L., Tsen, M., Dubnicoff, T., Danao, J., Liao, X. C., ... Wasserman, S. A. (1999). Impaired cytokine signaling in mice lacking the IL-1 receptor- associated kinase. Journal of Immunology, 163(2), 978-984.

Impaired cytokine signaling in mice lacking the IL-1 receptor- associated kinase. / Thomas, James A.; Allen, Jerry L.; Tsen, May; Dubnicoff, Todd; Danao, Jay; Liao, X. Charlene; Cao, Zhaodan; Wasserman, Steven A.

In: Journal of Immunology, Vol. 163, No. 2, 15.07.1999, p. 978-984.

Research output: Contribution to journalArticle

Thomas, JA, Allen, JL, Tsen, M, Dubnicoff, T, Danao, J, Liao, XC, Cao, Z & Wasserman, SA 1999, 'Impaired cytokine signaling in mice lacking the IL-1 receptor- associated kinase', Journal of Immunology, vol. 163, no. 2, pp. 978-984.
Thomas JA, Allen JL, Tsen M, Dubnicoff T, Danao J, Liao XC et al. Impaired cytokine signaling in mice lacking the IL-1 receptor- associated kinase. Journal of Immunology. 1999 Jul 15;163(2):978-984.
Thomas, James A. ; Allen, Jerry L. ; Tsen, May ; Dubnicoff, Todd ; Danao, Jay ; Liao, X. Charlene ; Cao, Zhaodan ; Wasserman, Steven A. / Impaired cytokine signaling in mice lacking the IL-1 receptor- associated kinase. In: Journal of Immunology. 1999 ; Vol. 163, No. 2. pp. 978-984.
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