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脂肪源基质细胞在“生理”缺氧条件下对 T 细胞的免疫抑制作用增强。

Adipose-derived stromal cell immunosuppression of T cells is enhanced under "physiological" hypoxia.

机构信息

Cell Physiology Laboratory, Institute of Biomedical Problems, Russian Academy of Sciences, Moscow, Russia.

Cell Physiology Laboratory, Institute of Biomedical Problems, Russian Academy of Sciences, Moscow, Russia.

出版信息

Tissue Cell. 2020 Apr;63:101320. doi: 10.1016/j.tice.2019.101320. Epub 2019 Dec 3.

DOI:10.1016/j.tice.2019.101320
PMID:32223948
Abstract

Multipotent mesenchymal stromal cells (MSCs) are characterized by immunomodulatory properties along with the high proliferative and paracrine activity, as well as multilineage potency. The effects of MSCs on the T cell adaptive immunity are of a special interest. Low O level (1-7 %) is known to be typical for the putative site of the MSC - T cell interactions. A comparative evaluation of the effects of adipose tissue derived MSC (ASCs) on the mitogen-stimulated T cells at the ambient (20 %) and tissue-related (5 %) O levels demonstrated reduced T cell activation by the HLA-DR expression, decreased pro-inflammatory and increased anti-inflammatory cytokine production in co-culture, inhibited T cell proliferation, with the effects increased at hypoxia. T cell interactions with ASCs resulted in the up-regulation of PDCD1, Foxp3, and TGFβ1 known to play an important role in the immune response suppression, and in the down-regulation of genes involved in the inflammatory reaction (IL2, IFNG). These changes were significantly increased under hypoxia. At the same time, neither ASCs nor the reduced O level had negative effects on the viability of T cells.

摘要

多能间充质基质细胞 (MSCs) 的特征是具有免疫调节特性,以及高增殖和旁分泌活性,以及多能性。MSCs 对 T 细胞适应性免疫的影响具有特殊的意义。已知 MSC-T 细胞相互作用的假定部位的 O 水平低(1-7%)。在环境(20%)和组织相关(5%)O 水平下,比较评估脂肪组织来源的 MSC (ASCs) 对有丝分裂原刺激的 T 细胞的影响,结果表明 HLA-DR 表达降低,共培养中促炎细胞因子产生减少,抗炎细胞因子产生增加,T 细胞增殖受到抑制,低氧时作用增强。T 细胞与 ASCs 的相互作用导致 PDCD1、Foxp3 和 TGFβ1 的上调,这些因子在免疫反应抑制中发挥重要作用,同时下调参与炎症反应的基因(IL2、IFNG)。在低氧条件下,这些变化显著增加。同时,无论是 ASCs 还是低 O 水平都没有对 T 细胞的活力产生负面影响。

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