CD109 on Dendritic Cells Regulates Airway Hyperreactivity and Eosinophilic Airway Inflammation
CD109 on Dendritic Cells Regulates Airway Hyperreactivity and Eosinophilic Airway Inflammation
复制标题
树突状细胞表面CD109调节气道高反应性和嗜酸性气道炎症
DOI：
10.1165/rcmb.2022-0109oc
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发表时间：
2023-02-01
影响因子：
6.4
通讯作者：
Suda, Takafumi
中科院分区：
文献类型：
--
作者：
Aono, Yuya;Suzuki, Yuzo;Suda, Takafumi
哮喘是一种慢性气道炎症性疾病，其特征是气道高反应性（AHR）和嗜酸粒细胞性气道炎症。树突状细胞 (DC) 通过呈递过敏原，导致 2 型辅助 T 细胞 (Th2) 偏斜和嗜酸性粒细胞炎症，对于哮喘的发生至关重要。最近的研究表明，CD109是一种糖基磷脂酰肌醇锚定的糖蛋白，参与类风湿性关节炎和牛皮癣等炎症性疾病的发病机制。然而，尚无研究探讨 CD109 在哮喘中的作用。本研究试图探讨 DC 上 CD109 在 AHR 和过敏性炎症发展中的作用。 CD109缺陷型小鼠(CD109(-/-))用屋尘螨或卵清蛋白致敏，并与野生型小鼠进行比较以诱导AHR和过敏性炎症。与野生型小鼠相比，CD109 缺陷小鼠的 AHR 和嗜酸性粒细胞炎症减少，并且 Th2 细胞因子表达降低。有趣的是，过敏激发后，CD109 表达在肺常规 DC2 (cDC2) 中被诱导，但在肺 cDC1 中不被诱导。 CD109(-/-) 小鼠的肺 cDC2 在高表达 RUNX3（runt 相关转录因子 3）的离体 DC-T 细胞共培养物中诱导细胞因子产生的能力较差，导致 Th2 分化受到抑制。负载屋尘螨的骨髓源性 CD109(-/-) DC 的过继转移未能产生 AHR 和嗜酸性粒细胞炎症。最后，单克隆抗 CD109 抗体的施用减少了气道嗜酸性粒细胞，并显着降低了 AHR。我们的结果表明 CD109 参与哮喘发病机制。 CD109是哮喘的新治疗靶点。
Asthma is a chronic airway inflammatory disease characterized by airway hyperreactivity (AHR) and eosinophilic airway inflammation. Dendritic cells (DCs) are essential for the development of asthma via presenting allergens, causing T-helper cell type 2 (Th2) skewing and eosinophil inflammation. Recent studies have revealed that CD109, a glycosylphosphatidylinositol-anchored glycoprotein, is involved in the pathogenesis of inflammatory diseases such as rheumatoid arthritis and psoriasis. However, no study has addressed the role of CD109 in asthma. This study sought to address the role of CD109 on DCs in the development of AHR and allergic inflammation. CD109-deficient mice (CD109(-/-)) were sensitized with house dust mite or ovalbumin and compared with wild-type mice for induction of AHR and allergic inflammation. CD109-deficient mice had reduced AHR and eosinophilic inflammation together with lower Th2 cytokine expression compared with wild-type mice. Interestingly, CD109 expression was induced in lung conventional DC2s (cDC2s), but not lung cDC1s, upon allergic challenge. Lung cDC2s from CD109(-/-) mice had a poor ability to induce cytokine production in ex vivo DC-T cell cocultures with high expression of RUNX3 (runt- related transcription factor 3), resulting in suppression of Th2 differentiation. Adoptive transfer of bone marrow-derived CD109(-/-) DCs loaded with house dust mite failed to develop AHR and eosinophilic inflammation. Finally, administration of monoclonal anti-CD109 antibody reduced airway eosinophils and significantly decreased AHR. Our results suggest the involvement of CD109 in asthma pathogenesis. CD109 is a novel therapeutic target for asthma.