Inhibitory function of two NFAT family members in lymphoid homeostasis and Th2 development

Immunity. 1998 Nov;9(5):627-35. doi: 10.1016/s1074-7613(00)80660-3.

Abstract

Nuclear factor of activated T cells (NFAT) is a critical regulator of early gene transcription in response to TCR-mediated signals. Here, we show that mice lacking both NFATp and NFAT4 develop a profound lymphoproliferative disorder likely due to a lowered threshold for TCR signaling coupled with increased resistance to apoptosis secondary to defective FasL expression. NFAT mutant mice also have allergic blepharitis, interstitial pneumonitis, and a 10(3) to 10(4) fold increase in serum IgG1 and IgE levels, secondary to a dramatic and selective increase in Th2 cytokines. This phenotype may be ascribed to unopposed occupancy of the IL-4 promoter by NFATc. Our data demonstrate that lymphoid homeostasis and Th2 activation require a critical balance among NFAT family members.

Publication types

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

MeSH terms

  • Alveolitis, Extrinsic Allergic / immunology
  • Alveolitis, Extrinsic Allergic / metabolism
  • Animals
  • Apoptosis / physiology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / physiology
  • Blepharitis / immunology
  • Blepharitis / metabolism
  • Cell Nucleus / metabolism
  • Cytokines / biosynthesis
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / physiology*
  • Fas Ligand Protein
  • Homeostasis / physiology*
  • Immunoglobulins / biosynthesis
  • Lung Diseases, Interstitial / immunology
  • Lung Diseases, Interstitial / metabolism
  • Lymphocyte Activation / physiology
  • Lymphoid Tissue / cytology
  • Lymphoid Tissue / immunology
  • Lymphoid Tissue / physiology*
  • Membrane Glycoproteins / biosynthesis
  • Mice
  • Mice, Inbred BALB C
  • NFATC Transcription Factors
  • Nuclear Proteins*
  • Receptors, Antigen, T-Cell / physiology
  • Signal Transduction / physiology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / physiology
  • Th2 Cells / immunology
  • Th2 Cells / metabolism
  • Th2 Cells / physiology*
  • Transcription Factors / biosynthesis
  • Transcription Factors / physiology*

Substances

  • Cytokines
  • DNA-Binding Proteins
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Immunoglobulins
  • Membrane Glycoproteins
  • NFATC Transcription Factors
  • Nfatc3 protein, mouse
  • Nuclear Proteins
  • Receptors, Antigen, T-Cell
  • Transcription Factors