Zhao Lu, Wu Wenliang, Chen Gongqi, Huang Chunli, Kong Weiqiang, Gu Wei, Jie Huiru, Yi Lingling, Zhen Guohua
Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Key Laboratory of Respiratory Diseases, National Health Commission of People's Republic of China, Wuhan, China.
Respir Res. 2025 May 10;26(1):181. doi: 10.1186/s12931-025-03252-3.
Macrophage M2 polarization plays a critical role in type 2 airway inflammation in asthma. We previously reported that serine peptidase inhibitor, clade B, member 10 (SERPINB10) promotes airway eosinophilic inflammation in asthma.
To investigate the role of SERPINB10 in macrophage M2 polarization and airway inflammation in asthma.
The expression of SERPINB10 was detected in bronchoalveolar lavage (BAL) cells from 15 control subjects and 36 asthma patients. Serpinb10 knockout mice and wild type mice were sensitized and challenged with ovalbumin (OVA). Macrophage polarization and airway inflammation were evaluated. An adoptive transfer experiment of Serpinb10-deficient macrophages to macrophage-depleted mice was performed to assess the effect of Serpinb10 deficiency in macrophages on the airway inflammation in the model. The role of SERPINB10 in the activation of IL-4 receptor (IL-4R) signaling pathway and macrophage M2 polarization was investigated in cell cultures.
SERPINB10 expression was markedly elevated in BAL cells from asthmatic patients, and was significantly correlated with fractional exhaled nitric oxide and CD206, a marker for macrophage M2 polarization. In the OVA-induced allergic airway inflammation mouse model, Serpinb10 deficiency significantly inhibited airway inflammation, mucous cell metaplasia and airway hyperresponsiveness. Moreover, Serpinb10 deficiency suppressed the expression of M2 markers including Cd206, Arg1 in mouse lung tissues and the protein levels of M2 macrophage effector cytokines including Ccl17 and Ccl22 in BAL fluid. Adoptive transfer of Serpinb10-deficient bone marrow-derived macrophages (BMDMs) to wild type mice depleted macrophages significantly suppressed the airway inflammation and mucous cell metaplasia. Mechanistically, SERPINB10 suppresses the degradation of IL-4Rα in macrophages, thereby upregulating the phosphorylation of Stat6 and Akt and leading to macrophage M2 polarization.
SERPINB10 promotes macrophage M2 polarization by suppressing IL-4Rα degradation and upregulating IL-4R signaling. SERPINB10 is a potential therapeutic target for asthma.
巨噬细胞M2极化在哮喘的2型气道炎症中起关键作用。我们之前报道过丝氨酸蛋白酶抑制剂B家族成员10（SERPINB10）促进哮喘中的气道嗜酸性粒细胞炎症。
研究SERPINB10在哮喘中巨噬细胞M2极化和气道炎症中的作用。
检测了15名对照受试者和36名哮喘患者支气管肺泡灌洗（BAL）细胞中SERPINB10的表达。用卵清蛋白（OVA）对Serpinb10基因敲除小鼠和野生型小鼠进行致敏和激发。评估巨噬细胞极化和气道炎症。进行了将Serpinb10缺陷型巨噬细胞过继转移至巨噬细胞耗竭小鼠的实验，以评估巨噬细胞中Serpinb10缺陷对模型中气道炎症的影响。在细胞培养中研究了SERPINB10在白细胞介素-4受体（IL-4R）信号通路激活和巨噬细胞M2极化中的作用。
哮喘患者BAL细胞中SERPINB10表达明显升高，且与呼出一氧化氮分数和巨噬细胞M2极化标志物CD206显著相关。在OVA诱导的过敏性气道炎症小鼠模型中，Serpinb10缺陷显著抑制气道炎症、黏液细胞化生和气道高反应性。此外，Serpinb10缺陷抑制了小鼠肺组织中包括Cd206、Arg1在内的M2标志物的表达以及BAL液中包括Ccl17和Ccl22在内的M2巨噬细胞效应细胞因子的蛋白水平。将Serpinb10缺陷的骨髓来源巨噬细胞（BMDM）过继转移至野生型巨噬细胞耗竭小鼠显著抑制了气道炎症和黏液细胞化生。机制上，SERPINB10抑制巨噬细胞中IL-4Rα的降解，从而上调Stat6和Akt的磷酸化并导致巨噬细胞M2极化。
SERPINB10通过抑制IL-4Rα降解和上调IL-4R信号促进巨噬细胞M2极化。SERPINB10是哮喘的一个潜在治疗靶点。
