Lee Cho-Rong, Kwak Yewon, Yang Taewoo, Han Jung Hyun, Park Sang-Heon, Ye Michael B, Lee Wongeun, Sim Kyu-Young, Kang Jung-Ah, Kim Yong-Chul, Mazmanian Sarkis K, Park Sung-Gyoo
School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea.
Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea.
Cell Rep. 2016 Dec 20;17(12):3219-3232. doi: 10.1016/j.celrep.2016.11.062.
Myeloid-derived suppressor cells (MDSCs) are well known regulators of regulatory T cells (Treg cells); however, the direct regulation of MDSCs by Treg cells has not been well characterized. We find that colitis caused by functional deficiency of Treg cells leads to altered expansion and reduced function of MDSCs. During differentiation of MDSCs in vitro from bone marrow cells, Treg cells enhanced MDSC function and controlled their differentiation through a mechanism involving transforming growth factor-β (TGF-β). TGF-β-deficient Treg cells were not able to regulate MDSC function in an experimentally induced model of colitis. Finally, we evaluated the therapeutic effect of TGF-β-mediated in-vitro-differentiated MDSCs on colitis. Adoptive transfer of MDSCs that differentiated with TGF-β led to better colitis prevention than the transfer of MDSCs that differentiated without TGF-β. Our results demonstrate an interaction between Treg cells and MDSCs that contributes to the regulation of MDSC proliferation and the acquisition of immunosuppressive functions.
髓源性抑制细胞（MDSCs）是调节性T细胞（Treg细胞）的著名调节因子；然而，Treg细胞对MDSCs的直接调节尚未得到充分表征。我们发现，Treg细胞功能缺陷引起的结肠炎会导致MDSCs的扩增改变和功能降低。在体外从骨髓细胞分化MDSCs的过程中，Treg细胞增强了MDSC功能，并通过一种涉及转化生长因子-β（TGF-β）的机制控制其分化。在实验性诱导的结肠炎模型中，缺乏TGF-β的Treg细胞无法调节MDSC功能。最后，我们评估了TGF-β介导的体外分化MDSCs对结肠炎的治疗效果。与未用TGF-β分化的MDSCs相比，用TGF-β分化的MDSCs的过继转移对结肠炎的预防效果更好。我们的结果表明，Treg细胞与MDSCs之间存在相互作用，这有助于调节MDSC增殖和获得免疫抑制功能。
