TY - JOUR
T1 - Impaired cytokine signaling in mice lacking the IL-1 receptor- associated kinase
AU - Thomas, James A.
AU - Allen, Jerry L.
AU - Tsen, May
AU - Dubnicoff, Todd
AU - Danao, Jay
AU - Liao, X. Charlene
AU - Cao, Zhaodan
AU - Wasserman, Steven A.
PY - 1999/7/15
Y1 - 1999/7/15
N2 - 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.
AB - 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.
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M3 - Article
C2 - 10395695
AN - SCOPUS:0033565779
SN - 0022-1767
VL - 163
SP - 978
EP - 984
JO - Journal of Immunology
JF - Journal of Immunology
IS - 2
ER -