Department of Otolaryngology, the Second Affiliated Hospital of the Naval Medical University (Shanghai Changzheng Hospital), Shanghai, China.
Department of Otolaryngology, Naval Medical Center, Naval Medical University, Shanghai, China.
J Allergy Clin Immunol. 2024 Sep;154(3):644-656. doi: 10.1016/j.jaci.2024.04.028. Epub 2024 May 16.
Previous studies implied that local M2 polarization of macrophage promoted mucosal edema and exacerbated T2 type inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP). However, the specific pathogenic role of M2 macrophages and the intrinsic regulators in the development of CRS remains elusive.
We sought to investigate the regulatory role of SIRT5 in the polarization of M2 macrophages and its potential contribution to the development of CRSwNP.
Real-time reverse transcription-quantitative PCR and Western blot analyses were performed to examine the expression levels of SIRT5 and markers of M2 macrophages in sinonasal mucosa samples obtained from both CRS and control groups. Wild-type and Sirt5-knockout mice were used to establish a nasal polyp model with T2 inflammation and to investigate the effects of SIRT5 in macrophage on disease development. Furthermore, in vitro experiments were conducted to elucidate the regulatory role of SIRT5 in polarization of M2 macrophages.
Clinical investigations showed that SIRT5 was highly expressed and positively correlated with M2 macrophage markers in eosinophilic polyps. The expression of SIRT5 in M2 macrophages was found to contribute to the development of the disease, which was impaired in Sirt5-deficient mice. Mechanistically, SIRT5 was shown to enhance the alternative polarization of macrophages by promoting glutaminolysis.
SIRT5 plays a crucial role in promoting the development of CRSwNP by supporting alternative polarization of macrophages, thus providing a potential target for CRSwNP interventions.
先前的研究表明，巨噬细胞的局部 M2 极化促进了鼻息肉慢性鼻窦炎（CRSwNP）中的黏膜水肿和 T2 型炎症加重。然而，M2 巨噬细胞的具体致病作用及其在 CRS 发展中的内在调节因子仍不清楚。
我们旨在研究 SIRT5 在 M2 巨噬细胞极化中的调节作用及其对 CRSwNP 发展的潜在贡献。
采用实时逆转录定量 PCR 和 Western blot 分析检测 SIRT5 及其 M2 巨噬细胞标志物在慢性鼻窦炎和对照组鼻黏膜样本中的表达水平。使用野生型和 Sirt5 敲除小鼠建立 T2 炎症性鼻息肉模型，以研究 SIRT5 在巨噬细胞中的作用对疾病发展的影响。此外，还进行了体外实验以阐明 SIRT5 在 M2 巨噬细胞极化中的调节作用。
临床研究表明，SIRT5 在嗜酸性息肉中高表达且与 M2 巨噬细胞标志物呈正相关。SIRT5 在 M2 巨噬细胞中的表达有助于疾病的发展，而 Sirt5 缺陷小鼠则会损害疾病的发展。机制上，SIRT5 通过促进谷氨酰胺分解代谢来增强巨噬细胞的替代极化。
SIRT5 通过支持巨噬细胞的替代极化在促进 CRSwNP 的发展中起着关键作用，从而为 CRSwNP 的干预提供了一个潜在的靶点。
