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

Liu, Yawei LU ; Carlsson, Robert LU ; Comabella, Manuel; Wang, Jun Yang; Kosicki, Michael; Carrion, Belinda; Hasan, Maruf LU ; Wu, Xudong; Montalban, Xavier and Dziegiel, Morten Hanefeld, et al. (2014) In Nature Medicine 20(3). p.272-282
Abstract

The defective generation or function of regulatory T (T reg) 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 T reg cell population, herein called FoxA1 + T reg cells. FoxA1 bound to the Pdl1 promoter, inducing programmed cell death ligand 1 (Pd-l1) expression, which was essential for the FoxA1 + T reg cells to kill activated T cells. FoxA1 + T reg 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... (More)

The defective generation or function of regulatory T (T reg) 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 T reg cell population, herein called FoxA1 + T reg cells. FoxA1 bound to the Pdl1 promoter, inducing programmed cell death ligand 1 (Pd-l1) expression, which was essential for the FoxA1 + T reg cells to kill activated T cells. FoxA1 + T reg 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 + T reg cells inhibited experimental autoimmune encephalomyelitis in a FoxA1-and Pd-l1-dependent manner. The development of FoxA1 + T reg cells is induced by interferon-β (IFN-β) and requires T cell-intrinsic IFN-α/β receptor (Ifnar) signaling, as the frequency of FoxA1 + T reg 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 + T reg 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 + T reg cells.

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Nature Medicine
volume
20
issue
3
pages
11 pages
publisher
Nature Publishing Group
external identifiers
  • scopus:84896116263
ISSN
1078-8956
DOI
10.1038/nm.3485
language
English
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no
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b09ef884-6eb6-485b-89db-97828df2ed3d
date added to LUP
2019-07-02 10:04:12
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2019-09-16 11:01:35
@article{b09ef884-6eb6-485b-89db-97828df2ed3d,
  abstract     = {<p>The defective generation or function of regulatory T (T reg) 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 T reg cell population, herein called FoxA1 + T reg cells. FoxA1 bound to the Pdl1 promoter, inducing programmed cell death ligand 1 (Pd-l1) expression, which was essential for the FoxA1 + T reg cells to kill activated T cells. FoxA1 + T reg 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 + T reg cells inhibited experimental autoimmune encephalomyelitis in a FoxA1-and Pd-l1-dependent manner. The development of FoxA1 + T reg cells is induced by interferon-β (IFN-β) and requires T cell-intrinsic IFN-α/β receptor (Ifnar) signaling, as the frequency of FoxA1 + T reg 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 + T reg 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 + T reg cells.</p>},
  author       = {Liu, Yawei and Carlsson, Robert and Comabella, Manuel and Wang, Jun Yang and Kosicki, Michael and Carrion, Belinda and Hasan, Maruf and Wu, Xudong and Montalban, Xavier and Dziegiel, Morten Hanefeld and Sellebjerg, Finn and Sørensen, Per Soelberg and Helin, Kristian and Issazadeh-Navikas, Shohreh},
  issn         = {1078-8956},
  language     = {eng},
  month        = {01},
  number       = {3},
  pages        = {272--282},
  publisher    = {Nature Publishing Group},
  series       = {Nature Medicine},
  title        = {FoxA1 directs the lineage and immunosuppressive properties of a novel regulatory T cell population in EAE and MS},
  url          = {http://dx.doi.org/10.1038/nm.3485},
  volume       = {20},
  year         = {2014},
}