Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen 91054, Germany.
J Immunol Res. 2019 Aug 14;2019:3161750. doi: 10.1155/2019/3161750. eCollection 2019.
Rheumatoid arthritis (RA) is a multifactorial autoimmune disease whose main hallmark is inflammation and destruction of the joints. Two cell types within the synovium that play an important role in RA are fibroblast-like synoviocytes (FLS) and macrophages. The latter innate immune cells show a high plasticity in their phenotype and are central in inflammatory processes. Low-dose radiotherapy (LD-RT) with particularly a single dose of 0.5 Gy has been demonstrated to have a positive impact on pain, inflammation, and bone in inflamed joints. We now examined for the first time how LD-RT influences FLS and bone marrow-derived macrophages in co-culture systems of an experimental model of RA to reveal further mechanisms of immune modulatory effects of low and intermediate dose of ionizing radiation. For this, the bone marrow of h tg mice was differentiated either with cytokines to obtain key macrophage phenotypes (M0, M1, and M2) or with supernatants (SN) of untreated or irradiated FLS. Flow cytometry analyses were used to analyse the impact of radiation (0.1, 0.5, 1.0, and 2.0 Gy) on the phenotype of macrophages in the presence or absence of SN of FLS. LD-RT had no impact on cytokine-mediated macrophage polarization in M0, M1, or M2 macrophages. However, SN of irradiated FLS particularly reduced CD206 expression on macrophages. Macrophage phenotype was stable when being in contact with SN of nonirradiated FLS, but significantly increased surface expression of CD206 and slightly decreased CD80 and CD86 expression were observed when macrophage themselves were irradiated with 0.5 Gy under these microenvironmental conditions, again highlighting discontinuous dose dependencies in the low and intermediate dose range. One can conclude that FLS-dependent microenvironmental conditions have a slight influence on the modulation of macrophage phenotype under radiation exposure conditions. Future studies are needed to reveal the impact of radiation exposure on the functions of treated macrophages under such microenvironmental conditions.
类风湿关节炎（RA）是一种多因素自身免疫性疾病，其主要特征是炎症和关节破坏。滑膜中两种细胞类型在 RA 中起着重要作用，成纤维样滑膜细胞（FLS）和巨噬细胞。后者先天免疫细胞在表型上显示出很高的可塑性，并且在炎症过程中起着核心作用。低剂量放射治疗（LD-RT），特别是单次 0.5Gy 的剂量，已被证明对炎症关节中的疼痛、炎症和骨骼有积极影响。我们现在首次检查了 LD-RT 如何影响实验性 RA 模型中的共培养系统中的 FLS 和骨髓来源的巨噬细胞，以揭示低剂量和中剂量电离辐射的免疫调节作用的进一步机制。为此，h tg 小鼠的骨髓用细胞因子分化，以获得关键的巨噬细胞表型（M0、M1 和 M2）或未经处理或辐照的 FLS 的上清液（SN）。流式细胞术分析用于分析辐射（0.1、0.5、1.0 和 2.0Gy）对存在或不存在 FLS SN 的情况下巨噬细胞表型的影响。LD-RT 对 M0、M1 或 M2 巨噬细胞中细胞因子介导的巨噬细胞极化没有影响。然而，辐照的 FLS 的 SN 特别降低了巨噬细胞上的 CD206 表达。当巨噬细胞与未辐照的 FLS 的 SN 接触时，巨噬细胞表型是稳定的，但当在这些微环境条件下自身受到 0.5Gy 的照射时，观察到 CD206 的表面表达显著增加，CD80 和 CD86 的表达略有减少，再次强调了低剂量和中剂量范围内的不连续剂量依赖性。可以得出结论，FLS 依赖性微环境条件对辐射暴露条件下巨噬细胞表型的调节有轻微影响。需要进一步的研究来揭示在这种微环境条件下辐射暴露对治疗后的巨噬细胞功能的影响。
