Xie Huanxia, Ji Jiang, Liu Zhichen, Lu Ning, Wei Yuqian, Zhou Aina, Liu Jisheng, Jiao Qingqing
Department of Ear, Nose, and Throat, The First Affiliated Hospital of Soochow University, Suzhou, China.
Department of Dermatology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
Front Immunol. 2025 Jan 7;15:1460104. doi: 10.3389/fimmu.2024.1460104. eCollection 2024.
Uncontrolled severe eosinophilic chronic rhinosinusitis (eCRS) is associated with elevated levels of Th2 cells and raised immunoglobulin concentrations in nasal polyp tissue. eCRS is characterized by high eosinophilic infiltration and type 2 inflammation. Gαi1/3 proteins participate in allergic inflammation by regulating immune cells. Whether Gαi1/3 proteins have a role in the development of eCRS remains unknown.
To investigate the association between Gαi1/3 expression levels and CRS and the underlying mechanisms.
Western blotting and immunohistology were used to detect Gαi1/3 expression. Correlations between Gαi1/3 and immune cells and clinical parameters were analyzed. Signaling pathway activation in IL-5-induced Gαi1/3-knockout or knockdown mouse embryonic fibroblasts (MEFs) and eosinophils (EoL-1 cells) was detected by western blotting. EdU/DAPI was used to evaluate the proliferation of EoL-1 cells. A CRS model was established using Gαi1/3-knockout mice, and histological analysis and inflammatory cytokine measurements were performed.
Compared with the non-eCRS subset, the eCRS subset showed significantly increased Gαi1/3 expression levels. High nasal tissue Gαi1/3 levels were linked to high tissue eosinophil infiltration, and high disease severity and allergic conditions in CRS patients. Gαi1/3 were required for IL-5-induced Akt-mTOR and Erk activation in MEFs. In EoL-1 cells, Gαi1/3 was associated with IL-5-activated IL-5Rα, promoting IL-5Rα endocytosis and transducing downstream signaling. IL-5-induced EoL-1 cell proliferation and degranulation were suppressed after Gαi1/3 silencing. In a CRS murine model, immune cell infiltration and type 2 inflammation were largely impaired in Gαi1/3-double-knockout mice.
Increased Gαi1/3 expression levels in nasal tissue are linked to eosinophil infiltration and increased disease severity in CRS patients. Gαi1/3 contributes to eosinophil activation and participates in regulating allergic inflammation in CRS patients.
未控制的严重嗜酸性粒细胞性慢性鼻-鼻窦炎（eCRS）与鼻息肉组织中Th2细胞水平升高和免疫球蛋白浓度升高有关。eCRS的特征是嗜酸性粒细胞高度浸润和2型炎症。Gαi1/3蛋白通过调节免疫细胞参与过敏性炎症。Gαi1/3蛋白在eCRS的发生发展中是否起作用尚不清楚。
研究Gαi1/3表达水平与CRS的关系及其潜在机制。
采用蛋白质免疫印迹法和免疫组织化学法检测Gαi1/3表达。分析Gαi1/3与免疫细胞及临床参数之间的相关性。通过蛋白质免疫印迹法检测IL-5诱导的Gαi1/3基因敲除或敲低的小鼠胚胎成纤维细胞（MEFs）和嗜酸性粒细胞（EoL-1细胞）中信号通路的激活情况。采用EdU/DAPI法评估EoL-1细胞的增殖。利用Gαi1/3基因敲除小鼠建立CRS模型，并进行组织学分析和炎症细胞因子检测。
与非eCRS亚组相比，eCRS亚组的Gαi1/3表达水平显著升高。鼻组织中Gαi1/3水平高与组织嗜酸性粒细胞浸润、CRS患者疾病严重程度高和过敏状态相关。在MEFs中，IL-5诱导的Akt-mTOR和Erk激活需要Gαi1/3。在EoL-1细胞中，Gαi1/3与IL-5激活的IL-5Rα相关，促进IL-5Rα内吞并转导下游信号。Gαi1/3沉默后，IL-5诱导的EoL-1细胞增殖和脱颗粒受到抑制。在CRS小鼠模型中，Gαi1/3双基因敲除小鼠的免疫细胞浸润和2型炎症在很大程度上受到损害。
鼻组织中Gαi1/3表达水平升高与CRS患者嗜酸性粒细胞浸润及疾病严重程度增加有关。Gαi1/3有助于嗜酸性粒细胞激活，并参与调节CRS患者的过敏性炎症。
