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Blood. 2017 Jul 20;130(3):348-359. doi: 10.1182/blood-2016-08-734244. Epub 2017 May 26.

T-cell expression of AhR inhibits the maintenance of pTreg cells in the gastrointestinal tract in acute GVHD.

Author information

1
Department of Microbiology and Immunology.
2
Lineberger Comprehensive Cancer Center, and.
3
Department of Laboratory Medicine and Pathology, University of North Carolina at Chapel Hill, Chapel Hill, NC.
4
National Cancer Institute, National Institutes of Health, Bethesda, MD.
5
University of Minnesota Comprehensive Cancer Center, Minneapolis, MN; and.
6
Department of Medicine and.
7
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC.

Abstract

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that affects the function and development of immune cells. Here, we show that recipient mice receiving AhR-/- T cells have improved survival and decreased acute graft-versus-host disease (aGVHD) in 2 different murine allogeneic bone marrow transplant (BMT) models. We also show that CD4+ T cells lacking AhR demonstrate reduced accumulation in secondary lymphoid tissue because of low levels of proliferation 4 days after BMT. Additionally, we found a significant increase in the quantity of peripherally induced regulatory donor T (pTreg) cells in the colon of recipients transplanted with AhR-/- T cells 14 days after transplant. Blockade of AhR using a clinically available AhR antagonist greatly enhanced the in vitro generation of inducible Treg (iTreg) cells from naïve CD4+ human T cells. We have identified AhR as a novel target on donor T cells that is critical to the pathogenesis of aGVHD.

PMID:
28550042
PMCID:
PMC5520467
DOI:
10.1182/blood-2016-08-734244
[Indexed for MEDLINE]
Free PMC Article

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