Targeted Disruption of the MyD88 Gene Results in Loss of IL-1- And IL-18-mediated Function

Immunity. 1998 Jul;9(1):143-50. doi: 10.1016/s1074-7613(00)80596-8.

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-gamma 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-kappaB 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Antigens, Differentiation*
  • COS Cells
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Cells, Cultured
  • Cytokines / physiology*
  • DNA / metabolism
  • Enzyme Activation
  • Female
  • Gene Targeting
  • Humans
  • Interleukin-1 / physiology*
  • Interleukin-18
  • JNK Mitogen-Activated Protein Kinases
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitogen-Activated Protein Kinases*
  • Myeloid Differentiation Factor 88
  • NF-kappa B / metabolism
  • Proteins / genetics
  • Proteins / physiology*
  • Receptors, Immunologic*
  • Th1 Cells / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Antigens, Differentiation
  • Cytokines
  • Interleukin-1
  • Interleukin-18
  • MYD88 protein, human
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • NF-kappa B
  • Proteins
  • Receptors, Immunologic
  • DNA
  • Calcium-Calmodulin-Dependent Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases