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Retinoic acid is essential for Th1 cell lineage stability and prevents transition to a Th17 cell program.

Immunity | 2015

CD4(+) T cells differentiate into phenotypically distinct T helper cells upon antigenic stimulation. Regulation of plasticity between these CD4(+) T-cell lineages is critical for immune homeostasis and prevention of autoimmune disease. However, the factors that regulate lineage stability are largely unknown. Here we investigate a role for retinoic acid (RA) in the regulation of lineage stability using T helper 1 (Th1) cells, traditionally considered the most phenotypically stable Th subset. We found that RA, through its receptor RARα, sustains stable expression of Th1 lineage specifying genes, as well as repressing genes that instruct Th17-cell fate. RA signaling is essential for limiting Th1-cell conversion into Th17 effectors and for preventing pathogenic Th17 responses in vivo. Our study identifies RA-RARα as a key component of the regulatory network governing maintenance and plasticity of Th1-cell fate and defines an additional pathway for the development of Th17 cells.

Pubmed ID: 25769610 RIS Download

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Associated grants

  • Agency: NCCIH NIH HHS, United States
    Id: R01 AT005382
  • Agency: NCI NIH HHS, United States
    Id: P30 CA023108
  • Agency: Medical Research Council, United Kingdom
    Id: MR/M003493/1
  • Agency: Medical Research Council, United Kingdom
    Id: MR/J006742/1
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI114059
  • Agency: NIAID NIH HHS, United States
    Id: R56 AI119062
  • Agency: Wellcome Trust, United Kingdom
  • Agency: NCCIH NIH HHS, United States
    Id: R01AT005382

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