Department of Dermatology, Xiangya Hospital of Central South University, Changsha, China; Hunan Key Laboratory of Aging Biology, Xiangya Hospital of Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital of Central South University, Changsha, China.
Henan Key Laboratory of Immunology and Targeted Therapy, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, China.
J Invest Dermatol. 2022 Jul;142(7):1835-1844.e2. doi: 10.1016/j.jid.2021.12.009. Epub 2021 Dec 22.
The infiltration of neutrophils is implicated in rosacea, which is a common chronic inflammatory facial disease. This study explores the biological function of neutrophils and their underlying mechanism in rosacea. A rosacea-like mouse model was established to explore the polarization of neutrophils. RNA sequencing was used to investigate the underlying mechanisms. Our results show that neutrophils partly switched to N2 phenotypes in both patients with rosacea and rosacea-like mouse models. The rosacea-like phenotype and inflammation in both a genetic mutation (Genista mice) and the Gr-1 antibody‒induced neutropenia mice were significantly aggravated compared with that in the control groups. In vitro, lipopolysaccharide + IFN-γ and IL4 stimulation of neutrophils successfully induced the N1 and N2 polarization of neutrophils, respectively. Replenishment of N2 neutrophils in the lesions of wild-type and Genista mice ameliorated the rosacea-like phenotype and inflammation. RNA sequencing suggested that N2 neutrophils relieved the rosacea-like phenotype, possibly by regulating the expression of blood circulation‒associated factors, such as ACE, AGTR2, and NOS1. Finally, N2 neutrophils regulated the proliferation of CD4 lymphocytes, which could explain the remission of inflammation in mice. Our results suggest that N2 polarization of neutrophils in rosacea exerts anti-inflammatory effects by regulating vascular factors and proliferation of CD4 T cells.
中性粒细胞浸润与酒渣鼻有关，酒渣鼻是一种常见的慢性炎症性面部疾病。本研究探讨了中性粒细胞的生物学功能及其在酒渣鼻中的作用机制。建立酒渣鼻样小鼠模型以探索中性粒细胞的极化。使用 RNA 测序研究潜在机制。我们的结果表明，在酒渣鼻患者和酒渣鼻样小鼠模型中，中性粒细胞部分向 N2 表型转换。与对照组相比，遗传突变（金雀花小鼠）和 Gr-1 抗体诱导中性粒细胞减少症小鼠的酒渣鼻样表型和炎症明显加重。体外实验表明，脂多糖+IFN-γ和 IL4 刺激中性粒细胞分别成功诱导 N1 和 N2 中性粒细胞极化。在野生型和金雀花小鼠的病变中补充 N2 中性粒细胞可改善酒渣鼻样表型和炎症。RNA 测序表明，N2 中性粒细胞通过调节 ACE、AGTR2 和 NOS1 等与血液循环相关的因子的表达来缓解酒渣鼻样表型。最后，N2 中性粒细胞调节 CD4 淋巴细胞的增殖，这可以解释小鼠炎症的缓解。我们的结果表明，酒渣鼻中性粒细胞的 N2 极化通过调节血管因子和 CD4 T 细胞的增殖发挥抗炎作用。
