First Author | Dant TA | Year | 2017 |
Journal | Blood | Volume | 130 |
Issue | 3 | Pages | 348-359 |
PubMed ID | 28550042 | Mgi Jnum | J:244401 |
Mgi Id | MGI:5913180 | Doi | 10.1182/blood-2016-08-734244 |
Citation | Dant TA, et al. (2017) T-cell expression of AhR inhibits the maintenance of pTreg cells in the gastrointestinal tract in acute GVHD. Blood 130(3):348-359 |
abstractText | 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 naive CD4+ human T cells. We have identified AhR as a novel target on donor T cells that is critical to the pathogenesis of aGVHD. |