NLRP10 is a NOD-like receptor essential to initiate adaptive immunity by dendritic cells

Nature. 2012 Apr 25;484(7395):510-3. doi: 10.1038/nature11012.

Abstract

NLRs (nucleotide-binding domain leucine-rich-repeat-containing receptors; NOD-like receptors) are a class of pattern recognition receptor (PRR) that respond to host perturbation from either infectious agents or cellular stress. The function of most NLR family members has not been characterized and their role in instructing adaptive immune responses remains unclear. NLRP10 (also known as PYNOD, NALP10, PAN5 and NOD8) is the only NLR lacking the putative ligand-binding leucine-rich-repeat domain, and has been postulated to be a negative regulator of other NLR members, including NLRP3 (refs 4-6). We did not find evidence that NLRP10 functions through an inflammasome to regulate caspase-1 activity nor that it regulates other inflammasomes. Instead, Nlrp10(-/-) mice had a profound defect in helper T-cell-driven immune responses to a diverse array of adjuvants, including lipopolysaccharide, aluminium hydroxide and complete Freund's adjuvant. Adaptive immunity was impaired in the absence of NLRP10 because of a dendritic cell (DC) intrinsic defect in emigration from inflamed tissues, whereas upregulation of DC costimulatory molecules and chemotaxis to CCR7-dependent and -independent ligands remained intact. The loss of antigen transport to the draining lymph nodes by a subset of migratory DCs resulted in an almost absolute loss in naive CD4(+) T-cell priming, highlighting the critical link between diverse innate immune stimulation, NLRP10 activity and the immune function of mature DCs.

Publication types

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

MeSH terms

  • Adaptive Immunity / immunology*
  • Adjuvants, Immunologic
  • Animals
  • Antigens / immunology
  • Apoptosis Regulatory Proteins / deficiency
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / immunology
  • Apoptosis Regulatory Proteins / metabolism*
  • Caspase 1
  • Cell Movement
  • Chemokines / immunology
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Gene Deletion
  • Inflammasomes
  • Ligands
  • Lymph Nodes / immunology
  • Mice
  • Mice, Inbred BALB C
  • T-Lymphocytes / immunology
  • T-Lymphocytes, Helper-Inducer / immunology
  • Vaccines / immunology

Substances

  • Adjuvants, Immunologic
  • Antigens
  • Apoptosis Regulatory Proteins
  • Chemokines
  • Inflammasomes
  • Ligands
  • NLRP10 protein, mouse
  • Vaccines
  • Caspase 1

Associated data

  • GEO/GSE36009