Student Research Committee, Kurdistan University of Medical Sciences, Sanandaj, Iran AND Department of Immunology and Hematology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran.
Department of Immunology and Hematology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran AND Cancer and Immunology Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran.
Iran J Allergy Asthma Immunol. 2020 Oct 18;19(5):484-496. doi: 10.18502/ijaai.v19i5.4464.
Co-inhibitory molecules modulate immune responses. Immunomodulatory properties of mesenchymal stem cells (MSCs) turn them into ideal candidates for cell therapy. This study was designed to investigate the immunomodulatory effect of adipose-derived stem cells (ASCs) on inflammatory environment of a co-culture of allogenic peripheral blood mononuclear cells (PBMCs) in a two-way mixed leukocyte reaction (twMLR) setting. ASCs were co-cultured with allogenic PBMCs in twMLR setting for four days. The proliferation of peripheral blood mononuclear cells (PBMCs), levels of interleukin (IL)-10, and expression of interferon-gamma (IFN-γ), B7-1, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed death-ligand 1 (PD-L1), +, and CD200R1 genes, as well as cell surface expression of CD200 and CD200R1, were measured in twMLR as control, and co-culture groups on days 0, 2 and 4 of the experiment. The proliferation of PBMCs was suppressed on days 2 and 4 of co-culture. The expression of CD200 (p=0.014), CD200R1, CTLA-4, and PD1 genes increased on days 2 and 4 of the co-culture compared to twMLR. CD200 expressing PBMCs decreased by 1.75% on day 2 of the co-culture but increased by 6.23% on day 4 of the co-culture (p=0.013) compared to the same days of twMLR. IL-10 levels increased in the co-culture supernatants on days 2 and 4 compared to twMLR (p<0.05). Our results showed that ASCs upregulate the CD200/CD200R1 axis more than PD-1/PD-L1 and CTLA-4/B7-1 pathways in the twMLR. Also, elevated expression of CD200R1 in the final day of co-culture was similar to PD-1 expression pattern. This finding suggests a role for the CD200/CD200R1 axis in later modulation of the immune response.
抑制性分子调节免疫反应。间充质干细胞（MSCs）的免疫调节特性使其成为细胞治疗的理想候选者。本研究旨在探讨脂肪来源干细胞（ASCs）在双向混合淋巴细胞反应（twMLR）环境中对同种异体外周血单个核细胞（PBMC）共培养的炎症环境的免疫调节作用。ASCs 与同种异体 PBMC 共培养 4 天。在 twMLR 中，在实验的第 0、2 和 4 天，测量外周血单个核细胞（PBMC）的增殖、白细胞介素（IL）-10 的水平以及干扰素-γ（IFN-γ）、B7-1、细胞毒性 T 淋巴细胞相关蛋白 4（CTLA-4）、程序性死亡配体 1（PD-L1）、+和 CD200R1 基因的表达以及 CD200 和 CD200R1 的细胞表面表达。与 twMLR 对照组相比，在共培养的第 2 和第 4 天，PBMC 的增殖受到抑制。与 twMLR 相比，在共培养的第 2 和第 4 天，CD200（p=0.014）、CD200R1、CTLA-4 和 PD1 基因的表达增加。在共培养的第 2 天，表达 CD200 的 PBMC 减少了 1.75%，但在共培养的第 4 天增加了 6.23%（p=0.013），与 twMLR 的相同天数相比。在共培养上清液中，与 twMLR 相比，IL-10 水平在第 2 和第 4 天增加（p<0.05）。我们的结果表明，与 PD-1/PD-L1 和 CTLA-4/B7-1 途径相比，ASCs 在 twMLR 中上调 CD200/CD200R1 轴。此外，在共培养的最后一天，CD200R1 的高表达与 PD-1 的表达模式相似。这一发现表明 CD200/CD200R1 轴在随后的免疫反应调节中发挥作用。
