M2 Phenotype Macrophages Colocalize with Schwann Cells in Human Dental Pulp
M2 Phenotype Macrophages Colocalize with Schwann Cells in Human Dental Pulp
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M2型巨噬细胞与雪旺细胞在人牙髓中的共定位
DOI：
10.1177/0022034519894957
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发表时间：
2020-01
影响因子：
7.6
通讯作者：
N. Yoshiba;N. Edanami;N. Ohkura;T. Maekawa;N. Takahashi;A. Tohma;K. Izumi;T. Maeda;A. Hosoya;H. Nakamura;K. Tabeta;Y. Noiri;K. Yoshiba
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文献类型：
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作者：
N. Yoshiba;N. Edanami;N. Ohkura;T. Maekawa;N. Takahashi;A. Tohma;K. Izumi;T. Maeda;A. Hosoya;H. Nakamura;K. Tabeta;Y. Noiri;K. Yoshiba
巨噬细胞是一种具有高度可塑性的免疫细胞，在组织损伤和修复中具有多种功能。它们通常分为两种功能表型：M1（促炎）和M2（抗炎和促愈合）。为了探讨巨噬细胞在人牙髓中的作用，我们研究了巨噬细胞在健康牙髓、三氧化二矿聚集体（mineral trioxide aggregate， MTA）盖髓修复过程和成人牙髓中巨噬细胞的定位和分布变化。我们还通过流式细胞分析定量了健康牙髓中M1/M2巨噬细胞的数量。健康全牙髓中CD68+CD86+细胞（M1表型）和CD68+CD163+细胞（M2表型）分别占CD68+细胞（泛巨噬细胞）（2.96%±0.41%）的2.11%±0.50%和44.99%±2.22%。有趣的是，M2型巨噬细胞与雪旺细胞在健康牙髓、矿化桥形成过程和体内龋齿感染牙髓中相关。此外，与雪旺细胞相关的M2巨噬细胞在所有体内条件下均表达脑源性神经营养因子（BDNF）。此外，我们发现浆细胞表达BDNF。从人牙髓分离的雪旺细胞与人单核细胞系THP-1共培养表明，雪旺细胞诱导THP-1细胞源性巨噬细胞M2表型极化。通过刺激与雪旺细胞保持接触的THP-1巨噬细胞，在共培养中导致其细胞形状延长和M2表型标记CD163的表达。综上所述，我们揭示了人类牙髓中巨噬细胞的时空定位和雪旺细胞对M2表型的有效诱导。M2巨噬细胞保护神经元件，而M1细胞促进神经元破坏。因此，通过雪旺细胞抑制巨噬细胞的神经破坏性M1表型和维持神经保护性M2表型可能是开发有效治疗策略以维持高度神经支配牙髓活力的关键。
Macrophages are immune cells with high plasticity that perform many functions related to tissue injury and repair. They are generally categorized as 2 functional phenotypes: M1 (proinflammatory) and M2 (anti-inflammatory and prohealing). To investigate the role of macrophages in human dental pulp, we examined the localization and distributional alterations of macrophages in healthy dental pulp as well as during the reparative process of pulp capping with mineral trioxide aggregate (MTA) and in cariously inflamed pulp of adult human teeth. We also quantified the populations of M1/M2 macrophages in healthy dental pulp by flow cytometric analysis. CD68+CD86+ cells (M1 phenotype) and CD68+CD163+ cells (M2 phenotype) were 2.11% ± 0.50% and 44.99% ± 2.22%, respectively, of 2.96% ± 0.41% CD68+ cells (pan-macrophages) in whole healthy dental pulp. Interestingly, M2 phenotype macrophages were associated with Schwann cells in healthy pulp, during mineralized bridge formation, and in pulp with carious infections in vivo. Furthermore, the M2 macrophages associated with Schwann cells expressed brain-derived neurotrophic factor (BDNF) under all in vivo conditions. Moreover, we found that plasma cells expressed BDNF. Coculture of Schwann cells isolated from human dental pulp and human monocytic cell line THP-1 showed that Schwann cells induced M2 phenotypic polarization of THP-1 cell-derived macrophages. The THP-1 macrophages that maintained contact with Schwann cells were stimulated, leading to elongation of their cell shape and expression of M2 phenotype marker CD163 in cocultures. In summary, we revealed the spatiotemporal localization of macrophages and potent induction of the M2 phenotype by Schwann cells in human dental pulp. M2 macrophages protect neural elements, whereas M1 cells promote neuronal destruction. Therefore, suppressing the neurodestructive M1 phenotype and maintaining the neuroprotective M2 phenotype of macrophages by Schwann cells may be critical for development of effective treatment strategies to maintain the viability of highly innervated dental pulp.