NBR1 is a new PB1 signalling adapter in Th2 differentiation and allergic airway inflammation in vivo

EMBO J. 2010 Oct 6;29(19):3421-33. doi: 10.1038/emboj.2010.214. Epub 2010 Aug 31.

Abstract

Allergic airway inflammation is a disease in which T helper 2 (Th2) cells have a critical function. The molecular mechanisms controlling Th2 differentiation and function are of paramount importance in biology and immunology. Recently, a network of PB1-containing adapters and kinases has been shown to be essential in this process owing to its function in regulating cell polarity and the activation of critical transcription factors. Here, we show in vivo data showing that T-cell-specific NBR1-deficient mice show impaired lung inflammation and have defective Th2 differentiation ex vivo with alterations in T-cell polarity and the selective inhibition of Gata3 and nuclear factor of activated T c1 activation. These results establish NBR1 as a novel PB1 adapter in Th2 differentiation and asthma.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing / immunology
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Alum Compounds / toxicity
  • Animals
  • Blotting, Western
  • Cell Differentiation / immunology*
  • Cell Polarity / immunology
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • GATA3 Transcription Factor / antagonists & inhibitors
  • Humans
  • Immunoprecipitation
  • Intracellular Signaling Peptides and Proteins
  • Jurkat Cells
  • Mice
  • Mice, Knockout
  • NFATC Transcription Factors / metabolism
  • Ovalbumin / toxicity
  • Polymerase Chain Reaction
  • Proteins / genetics
  • Proteins / immunology
  • Proteins / metabolism*
  • Respiratory Hypersensitivity / chemically induced
  • Respiratory Hypersensitivity / genetics
  • Respiratory Hypersensitivity / immunology*
  • Signal Transduction / physiology*
  • Th2 Cells / immunology*
  • Th2 Cells / physiology

Substances

  • Adaptor Proteins, Signal Transducing
  • Alum Compounds
  • GATA3 Transcription Factor
  • Gata3 protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • NFATC Transcription Factors
  • Nbr1 protein, mouse
  • Proteins
  • ovalbumin-alum
  • Ovalbumin