Human Primary Immune Cells Exhibit Distinct Mechanical Properties that Are Modified by Inflammation

Human Primary Immune Cells Exhibit Distinct Mechanical Properties that Are Modified by Inflammation
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DOI:
10.1016/j.bpj.2015.03.047
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发表时间:
2015-05-05
影响因子:
3.4
通讯作者:
Asnacios, Atef
Asnacios, Atef
中科院分区:
生物学3区
文献类型:
--
作者:
Bufi, Nathalie;Saitakis, Michael;Asnacios, Atef

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T淋巴细胞是免疫反应的关键调节器。它们的激活需要与免疫系统中不同的髓系细胞群相互作用,称为抗原提呈细胞(APC)。尽管T淋巴细胞最近被证明对机械提示,特别是对其环境的僵硬做出反应,但对APC的僵硬知之甚少。在本研究中,采用单细胞微板法测定了不同来源的人髓系原始APC,即单核细胞(ms,储存模数为520+90/-80 pA)、树突状细胞(DC,440+110/-90 pA)和巨噬细胞(MPH,900+110/-100 pA)的粘弹性系数。炎症条件调节了这些特性,存储模数从190帕到1450帕。炎症对力学性能的影响不依赖于常用的APC成熟标志物的诱导表达,这使得髓系APC僵硬成为炎症的另一个特征。此外,人T淋巴细胞的刚性低于所有受试的髓系细胞,也是最低的报道之一(杨氏模数为85+/-5pa)。最后,髓系细胞的粘弹性特性取决于它们的丝状肌动蛋白含量和肌球蛋白IIA活性,尽管这些参数的相对贡献因细胞类型而异。这些结果表明,T淋巴细胞在体内与髓系APC相互作用时面临不同的细胞刚性,这种机械格局在炎症条件下发生了变化。
T lymphocytes are key modulators of the immune response. Their activation requires cell-cell interaction with different myeloid cell populations of the immune system called antigen-presenting cells (APCs). Although T lymphocytes have recently been shown to respond to mechanical cues, in particular to the stiffness of their environment, little is known about the rigidity of APCs. In this study, single-cell microplate assays were performed to measure the viscoelastic moduli of different human myeloid primary APCs, i.e., monocytes (Ms, storage modulus of 520 +90/-80 Pa), dendritic cells (DCs, 440 +110/-90 Pa), and macrophages (MPHs, 900 +110/-100 Pa). Inflammatory conditions modulated these properties, with storage moduli ranging from 190 Pa to 1450 Pa. The effect of inflammation on the mechanical properties was independent of the induction of expression of commonly used APC maturation markers, making myeloid APC rigidity an additional feature of inflammation. In addition, the rigidity of human T lymphocytes was lower than that of all myeloid cells tested and among the lowest reported (Young's modulus of 85 +/- 5 Pa). Finally, the viscoelastic properties of myeloid cells were dependent on both their filamentous actin content and myosin IIA activity, although the relative contribution of these parameters varied within cell types. These results indicate that T lymphocytes face different cell rigidities when interacting with myeloid APCs in vivo and that this mechanical landscape changes under inflammation.