Format

Send to:

Choose Destination
See comment in PubMed Commons below
Nat Med. 2014 Mar;20(3):272-82. doi: 10.1038/nm.3485. Epub 2014 Feb 16.

FoxA1 directs the lineage and immunosuppressive properties of a novel regulatory T cell population in EAE and MS.

Author information

  • 1Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
  • 2Centre d'Esclerosi Múltiple de Catalunya (CEM-Cat), Unitat de Neuroimmunologia Clínica, Hospital Universitari Vall d´Hebron (HUVH)-Universitat Autònoma de Barcelona, Barcelona, Spain.
  • 3Blood Bank, Copenhagen University Hospital, Copenhagen, Denmark.
  • 4Danish Multiple Sclerosis Center, University of Copenhagen and Department of Neurology, Rigshospitalet, Copenhagen, Denmark.

Abstract

The defective generation or function of regulatory T (Treg) cells in autoimmune disease contributes to chronic inflammation and tissue injury. We report the identification of FoxA1 as a transcription factor in T cells that, after ectopic expression, confers suppressive properties in a newly identified Treg cell population, herein called FoxA1(+) Treg cells. FoxA1 bound to the Pdl1 promoter, inducing programmed cell death ligand 1 (Pd-l1) expression, which was essential for the FoxA1(+) Treg cells to kill activated T cells. FoxA1(+) Treg cells develop primarily in the central nervous system in response to autoimmune inflammation, have a distinct transcriptional profile and are CD4(+)FoxA1(+)CD47(+)CD69(+)PD-L1(hi)FoxP3(-). Adoptive transfer of stable FoxA1(+) Treg cells inhibited experimental autoimmune encephalomyelitis in a FoxA1-and Pd-l1-dependent manner. The development of FoxA1(+) Treg cells is induced by interferon-β (IFN-β) and requires T cell-intrinsic IFN-α/β receptor (Ifnar) signaling, as the frequency of FoxA1(+) Treg cells was reduced in Ifnb(-/-) and Ifnar(-/-) mice. In individuals with relapsing-remitting multiple sclerosis, clinical response to treatment with IFN-β was associated with an increased frequency of suppressive FoxA1(+) Treg cells in the blood. These findings suggest that FoxA1 is a lineage-specification factor that is induced by IFN-β and supports the differentiation and suppressive function of FoxA1(+) Treg cells.

PMID:
24531377
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group
    Loading ...
    Write to the Help Desk