期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 38, 期 3, 页码 870-876出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/eji.200737429
关键词
IL-1R-associated kinase 4; inflammation; LPS; T cells
类别
Interleukin-1 receptor-associated kinase (IRAK-4 is a serine-threonine kinase that plays an important role in innate and adaptive immune responses. While the requirement of IRAK-4 kinase activity has been studied in the context of IL-1R signaling, it is not clear whether IRAK-4 requires its kinase function for all of its roles in the immune system. IRAK-4 kinase-dead knock-in (IRAK-4KD/KD) mice were generated to further elucidate whether IRAK-4 kinase activity is required for IRAK-4 to induce cytokine production. IRAK-4KD/KD mice were impaired in their ability to produce cytokines in response to in vivo challenge with lipopolysaccharide (LPS), a potent TLR4 ligand. Cytokine production was also reduced in macrophages and dendritic cells from IRAK-4KD/KD mice in response to LPS and other TLR ligands. In addition, adaptive immune responses were impaired in IRAK-4KD/KD mice. Although in vitro T cell proliferation in response to TCR activation was unaffected in IRAK-4-deficient mice, in vivo T cell responses to lymphocytic choriomeningitits virus infection were significantly impaired in IRAK-4-knockout mice or mice expressing the kinase-dead mutant of IRAK-4. Collectively, these results indicate that IRAK-4 kinase activity is required for IRAK-4-dependent signaling in innate and adaptive immunity.
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