PI3K and negative regulation of TLR signaling

Trends Immunol. 2003 Jul;24(7):358-63. doi: 10.1016/s1471-4906(03)00139-x.


Excessive immune responses are detrimental to the host and negative feedback regulation is crucial for the maintenance of immune-system integrity. Recent studies have shown that phosphoinositide 3-kinase (PI3K) is an endogenous suppressor of interleukin-12 (IL-12) production triggered by Toll-like receptor (TLR) signaling and limits excessive Th1 polarization. Unlike IRAK-M (IL-1 receptor-associated kinase-M) and SOCS-1 (suppressor of cytokine signaling-1) that are induced by TLR signaling and function during the second or continuous exposure to stimulation, PI3K functions at the early phase of TLR signaling and modulates the magnitude of the primary activation. Thus, PI3K, IRAK-M and SOCS-1 have unique roles in the gate-keeping system, preventing excessive innate immune responses.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Feedback
  • Humans
  • Immunity, Innate
  • Interleukin-1 Receptor-Associated Kinases
  • Interleukin-12 / biosynthesis
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Models, Immunological
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Protein Kinases / metabolism
  • Receptors, Cell Surface / metabolism*
  • Signal Transduction
  • Th1 Cells / immunology
  • Toll-Like Receptors


  • Membrane Glycoproteins
  • Receptors, Cell Surface
  • Toll-Like Receptors
  • Interleukin-12
  • Protein Kinases
  • Phosphatidylinositol 3-Kinases
  • IRAK3 protein, human
  • Interleukin-1 Receptor-Associated Kinases
  • Irak3 protein, mouse