Sprenger-Svačina Alina, Svačina Martin K R, Gao Tong, Ritzel Rodney M, McCullough Louise D, Sheikh Kazim A, Zhang Gang
Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, United States.
Department of Neurology, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany.
Front Immunol. 2024 Nov 19;15:1487788. doi: 10.3389/fimmu.2024.1487788. eCollection 2024.
The current study focuses on understanding the functional role of different subsets of endoneurial macrophages in autoimmune polyneuropathies (AP) and traumatic peripheral nerve injury (TPNI), which holds potential for clinical application. Recent studies have advanced our understanding of the diverse origins of macrophages within peripheral nerves. However, there remains a gap in our knowledge regarding how endoneurial macrophages from different origins affect disease progression in AP versus TPNI.
Flow cytometry was utilized to analyze macrophage phenotypes, including polarization states, cytokine production, and myelin phagocytosis in animal models of AP and TPNI. This study focuses on two distinct origins of macrophages, namely CD11bF4/80 tissue-resident (TRM) and CD11bF4/80 blood-derived macrophages (BDM). The study utilized two animal models: the first was the spontaneous autoimmune peripheral polyneuropathy (SAPP) model in B7.2-null non-obese diabetic (NOD-B7.2-/-) mice, which serves as a model for inflammatory demyelinating polyneuropathy; the second model involved wild type C57BL/6 mice subjected to sciatic nerve crush injury, modeling TPNI. Behavioral, electrophysiological, and histological analyses were performed to assess peripheral nerve injury.
The study found that pro-inflammatory M1 macrophage polarization and tumor necrosis factor-alpha production by macrophages were more pronounced in the peripheral nerves of SAPP mice compared to those with TPNI, with the majority of these macrophages being TRM. In contrast, endoneurial macrophages in mice with TPNI were mainly BDM, exhibiting a less defined macrophage polarization and cytokine profile than TRM in AP mice. Interestingly, myelin phagocytosis was primarily driven by BDM in both SAPP and TPNI mice.
This study offers novel insights into origin-dependent macrophage functions in AP and TPNI. Furthermore, these findings may help the future development of novel therapies targeting macrophage subsets of specific origin in AP and TPNI.
当前的研究聚焦于理解神经内膜巨噬细胞不同亚群在自身免疫性多发性神经病（AP）和创伤性周围神经损伤（TPNI）中的功能作用，这具有临床应用潜力。近期研究增进了我们对周围神经内巨噬细胞多样起源的理解。然而，关于不同起源的神经内膜巨噬细胞如何影响AP与TPNI中的疾病进展，我们的认知仍存在空白。
运用流式细胞术分析AP和TPNI动物模型中巨噬细胞的表型，包括极化状态、细胞因子产生及髓鞘吞噬作用。本研究聚焦于巨噬细胞的两个不同起源，即CD11bF4/80组织驻留巨噬细胞（TRM）和CD11bF4/80血源巨噬细胞（BDM）。该研究使用了两种动物模型：第一种是B7.2基因缺失的非肥胖糖尿病（NOD-B7.2-/-）小鼠的自发性自身免疫性周围神经病（SAPP）模型，其作为炎性脱髓鞘性多发性神经病的模型；第二种模型是对野生型C57BL/6小鼠进行坐骨神经挤压伤，模拟TPNI。进行行为学、电生理学和组织学分析以评估周围神经损伤。
研究发现，与TPNI小鼠相比，SAPP小鼠周围神经中促炎性M1巨噬细胞极化及巨噬细胞产生肿瘤坏死因子-α更为明显，这些巨噬细胞大多数为TRM。相比之下，TPNI小鼠的神经内膜巨噬细胞主要是BDM，与AP小鼠中的TRM相比，其巨噬细胞极化和细胞因子谱不太明确。有趣的是，在SAPP和TPNI小鼠中，髓鞘吞噬主要由BDM驱动。
本研究为AP和TPNI中依赖起源的巨噬细胞功能提供了新见解。此外，这些发现可能有助于未来开发针对AP和TPNI中特定起源巨噬细胞亚群的新型疗法。
