Dant Trisha A, Lin Kaifeng L, Bruce Danny W, Montgomery Stephanie A, Kolupaev Oleg V, Bommiasamy Hemamalini, Bixby Lisa M, Woosley John T, McKinnon Karen P, Gonzalez Frank J, Blazar Bruce R, Vincent Benjamin G, Coghill James M, Serody Jonathan S
Department of Microbiology and Immunology.
Lineberger Comprehensive Cancer Center, and.
Blood. 2017 Jul 20;130(3):348-359. doi: 10.1182/blood-2016-08-734244. Epub 2017 May 26.
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 (pT) 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 T (iT) 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.
芳烃受体（AhR）是一种配体激活的转录因子，可影响免疫细胞的功能和发育。在此，我们表明，在两种不同的小鼠同种异体骨髓移植（BMT）模型中，接受AhR T细胞的受体小鼠存活率提高，急性移植物抗宿主病（aGVHD）减轻。我们还表明，缺乏AhR的CD4 T细胞在BMT后4天由于增殖水平低而在次级淋巴组织中的积累减少。此外，我们发现移植后14天，接受AhR T细胞移植的受体结肠中外周诱导调节性供体T（pT）细胞数量显著增加。使用临床可用的AhR拮抗剂阻断AhR可极大地增强从幼稚CD4人T细胞体外诱导生成诱导性T（iT）细胞。我们已确定AhR是供体T细胞上的一个新靶点，对aGVHD的发病机制至关重要。
