thapsigargin and Mucocutaneous-Lymph-Node-Syndrome

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.

Topics: Antigens, Differentiation; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Cycle Proteins; Cell Differentiation; Cinnamates; Clone Cells; Endoplasmic Reticulum; Endoplasmic Reticulum Chaperone BiP; Eukaryotic Initiation Factor-2; Forkhead Transcription Factors; Gene Expression; Heat-Shock Proteins; Humans; Interferon-gamma; Interleukin-10; Interleukin-23 Subunit p19; Mucocutaneous Lymph Node Syndrome; Protein Phosphatase 1; Stress, Physiological; T-Lymphocytes, Regulatory; Thapsigargin; Thiourea; Transcription Factor CHOP; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha; Up-Regulation