Masuda Junko, Takayama Eiji, Ichinohe Tatsuo, Strober Warren, Mizuno-Kamiya Masako, Ikawa Tomokatsu, Kitani Atsushi, Kawaki Harumi, Fuss Ivan, Kawamoto Hiroshi, Seno Akimasa, Vaidyanath Arun, Umemura Naoki, Mizutani Akifumi, Kasai Tomonari, Honjo Yasuko, Satoh Ayano, Murakami Hiroshi, Katsura Yoshimoto, Kondoh Nobuo, Seno Masaharu
Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University, Okayama 700-8530, Japan.
Laboratory of Host Defenses, Mucosal Immunity Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Exp Ther Med. 2018 Nov;16(5):4277-4282. doi: 10.3892/etm.2018.6689. Epub 2018 Sep 4.
Administration of bone marrow-derived mesenchymal stem cells (MSCs) is a possible treatment for graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation and other inflammatory conditions. To address the mechanism of immunosuppression by MSCs, in particular those derived from adipose tissue (AMSCs), AMSCs were isolated from three different mouse strains, and the suppressive capacity of the AMSCs thus obtained to suppress interferon (IFN)-γ generation in mixed lymphocyte reaction cultures serving as an model of GVHD were assessed. It was revealed that the AMSCs had a potent capacity to suppress IFN-γ production regardless of their strain of origin and that such suppression was not associated with production of interleukin-10. In addition, the results demonstrated that β2-microglobulin (β2m)-deficient AMSCs from β2m mice were also potent suppressor cells, verifying the fact that the mechanism underlying the suppression by AMSCs is independent of major histocompatibility complex (MHC) class I expression or MHC compatibility. As AMSCs appear to have immunosuppressive properties, AMSCs may be a useful source of biological suppressor cells for the control of GVHD in humans.
骨髓间充质干细胞（MSCs）的应用是同种异体造血干细胞移植后移植物抗宿主病（GVHD）及其他炎症性疾病的一种可能治疗方法。为了探究MSCs，特别是脂肪组织来源的间充质干细胞（AMSCs）的免疫抑制机制，从三种不同小鼠品系中分离出AMSCs，并评估所获得的AMSCs在作为GVHD模型的混合淋巴细胞反应培养物中抑制干扰素（IFN）-γ产生的抑制能力。结果显示，无论其来源品系如何，AMSCs都具有强大的抑制IFN-γ产生的能力，且这种抑制与白细胞介素-10的产生无关。此外，结果表明来自β2m基因敲除小鼠的β2微球蛋白（β2m）缺陷型AMSCs也是有效的抑制细胞，证实了AMSCs的抑制机制独立于主要组织相容性复合体（MHC）I类表达或MHC相容性这一事实。由于AMSCs似乎具有免疫抑制特性，它们可能是用于控制人类GVHD的生物抑制细胞的有用来源。
