| First Author | Thomas JA | Year | 1999 |
| Journal | J Immunol | Volume | 163 |
| Issue | 2 | Pages | 978-84 |
| PubMed ID | 10395695 | Mgi Jnum | J:56156 |
| Mgi Id | MGI:1340165 | Doi | 10.4049/jimmunol.163.2.978 |
| Citation | Thomas JA, et al. (1999) Impaired cytokine signaling in mice lacking the IL-1 receptor-associated kinase. J Immunol 163(2):978-84 |
| abstractText | 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-kappaB, 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-kappaB when stimulated with IL-1. Immune effector cells without IRAK exhibit a defective IFN-gamma 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. |
