Signaling via the RIP2 adaptor protein in central nervous system-infiltrating dendritic cells promotes inflammation and autoimmunity

Immunity. 2011 Jan 28;34(1):75-84. doi: 10.1016/j.immuni.2010.12.015. Epub 2011 Jan 13.

Abstract

Peripheral peptidolgycan (PGN) is present within antigen-presenting cells in the central nervous system (CNS) of multiple sclerosis (MS) patients, possibly playing a role in neuroinflammation. Accordingly, PGN is linked with disease progression in the animal model of MS, experimental autoimmune encephalomyelitis (EAE), but the role of specific PGN-sensing proteins is unknown. Here we report that the progression of EAE was dependent on the intracellular PGN sensors NOD1 and NOD2 and their common downstream adaptor molecule, receptor interacting protein 2 (RIP2; also known as RIPK2 and RICK). We found that RIP2, but not toll-like receptor 2 (TLR2), played a critical role in the activation of CNS-infiltrating dendritic cells. Our results suggest that PGN in the CNS is involved in the pathogenesis of EAE through the activation of infiltrating dendritic cells via NOD1-, NOD2-, and RIP2-mediated pathways.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / genetics
  • Cells, Cultured
  • Central Nervous System / immunology*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism*
  • Dendritic Cells / pathology
  • Disease Models, Animal
  • Disease Progression
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / physiopathology
  • Humans
  • Inflammation
  • Mice
  • Mice, Knockout
  • Multiple Sclerosis / immunology*
  • Nod1 Signaling Adaptor Protein / genetics
  • Nod1 Signaling Adaptor Protein / immunology
  • Nod1 Signaling Adaptor Protein / metabolism
  • Nod2 Signaling Adaptor Protein / genetics
  • Nod2 Signaling Adaptor Protein / immunology
  • Nod2 Signaling Adaptor Protein / metabolism
  • Prostaglandins / immunology
  • Prostaglandins / metabolism
  • Receptor-Interacting Protein Serine-Threonine Kinases / genetics
  • Receptor-Interacting Protein Serine-Threonine Kinases / immunology
  • Receptor-Interacting Protein Serine-Threonine Kinases / metabolism*
  • Signal Transduction / genetics
  • Signal Transduction / immunology

Substances

  • Nod1 Signaling Adaptor Protein
  • Nod1 protein, mouse
  • Nod2 Signaling Adaptor Protein
  • Nod2 protein, mouse
  • Prostaglandins
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • Ripk2 protein, mouse