[HTML][HTML] Targeted disruption of the MyD88 gene results in loss of IL-1-and IL-18-mediated function

O Adachi, T Kawai, K Takeda, M Matsumoto, H Tsutsui… - Immunity, 1998 - cell.com
O Adachi, T Kawai, K Takeda, M Matsumoto, H Tsutsui, M Sakagami, K Nakanishi, S Akira
Immunity, 1998cell.com
MyD88, originally isolated as a myeloid differentiation primary response gene, is shown to
act as an adaptor in interleukin-1 (IL-1) signaling by interacting with both the IL-1 receptor
complex and IL-1 receptor–associated kinase (IRAK). Mice generated by gene targeting to
lack MyD88 have defects in T cell proliferation as well as induction of acute phase proteins
and cytokines in response to IL-1. Increases in interferon-γ production and natural killer cell
activity in response to IL-18 are abrogated. In vivo Th1 response is also impaired …
Abstract
MyD88, originally isolated as a myeloid differentiation primary response gene, is shown to act as an adaptor in interleukin-1 (IL-1) signaling by interacting with both the IL-1 receptor complex and IL-1 receptor–associated kinase (IRAK). Mice generated by gene targeting to lack MyD88 have defects in T cell proliferation as well as induction of acute phase proteins and cytokines in response to IL-1. Increases in interferon-γ production and natural killer cell activity in response to IL-18 are abrogated. In vivo Th1 response is also impaired. Furthermore, IL-18-induced activation of NF-κB and c-Jun N-terminal kinase (JNK) is blocked in MyD88−/− Th1-developing cells. Taken together, these results demonstrate that MyD88 is a critical component in the signaling cascade that is mediated by IL-1 receptor as well as IL-18 receptor.
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