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 journalArticlepeer-review

244 Scopus citations


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
Issue number2
StatePublished - Jul 15 1999

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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