Endoplasmic reticulum stress drives a regulatory phenotype in human T-cell clones

Cell Immunol. 2010;266(1):1-6. doi: 10.1016/j.cellimm.2010.09.006. Epub 2010 Sep 24.

Abstract

T cells alter their functional phenotype during the evolution of an immune response (intra-lineage differentiation), but the driving forces to this plastic intra-lineage differentiation are poorly understood. The endoplasmic reticulum (ER) stress response is a possible critical event for the initial T cell differentiation upon antigen recognition. Here we studied the relationship between ER and Il-10 transcription in human Treg clones. The induction of ER stress with a canonical stressor, thapsigargin, enhances Il-10 transcription. Salubrinal, a small molecule inhibitor of the eukaryotic translation initiation factor 2α (eIF2α) dephosphporylation, dramatically inhibits it. Il-10 transcription is also enhanced by exogenous TNFα. These results disclose a role for ER stress in driving T cell plasticity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antigens, Differentiation / genetics
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Cycle Proteins / genetics
  • Cell Differentiation / immunology*
  • Cinnamates / pharmacology
  • Clone Cells
  • Endoplasmic Reticulum / drug effects
  • Endoplasmic Reticulum / immunology*
  • Endoplasmic Reticulum Chaperone BiP
  • Eukaryotic Initiation Factor-2 / antagonists & inhibitors
  • Forkhead Transcription Factors / genetics
  • Gene Expression / drug effects
  • Gene Expression / genetics
  • Heat-Shock Proteins / genetics
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism
  • Interleukin-23 Subunit p19 / genetics
  • Mucocutaneous Lymph Node Syndrome / immunology
  • Protein Phosphatase 1
  • Stress, Physiological / immunology*
  • T-Lymphocytes, Regulatory / cytology*
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • Thapsigargin / pharmacology
  • Thiourea / analogs & derivatives
  • Thiourea / pharmacology
  • Transcription Factor CHOP / genetics
  • Transforming Growth Factor beta / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology
  • Up-Regulation / genetics

Substances

  • Antigens, Differentiation
  • Cell Cycle Proteins
  • Cinnamates
  • DDIT3 protein, human
  • Endoplasmic Reticulum Chaperone BiP
  • Eukaryotic Initiation Factor-2
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Heat-Shock Proteins
  • IL10 protein, human
  • IL23A protein, human
  • Interleukin-23 Subunit p19
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • salubrinal
  • Interleukin-10
  • Transcription Factor CHOP
  • Thapsigargin
  • Interferon-gamma
  • PPP1R15A protein, human
  • Protein Phosphatase 1
  • Thiourea