Shanghai Research Institute of Acupuncture and Meridian, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China.
Cell Mol Life Sci. 2024 Jul 30;81(1):321. doi: 10.1007/s00018-024-05368-z.
Allergic asthma is a complex inflammatory disorder predominantly orchestrated by T helper 2 (Th2) lymphocytes. The anti-inflammatory protein Clara Cell 10-kDa (CC10), also known as secretoglobin family 1A member 1 (SCGB1A1), shows promise in modulating respiratory diseases. However, its precise role in asthma remains unclear. This study examines the potential of CC10 to suppress allergic asthma inflammation, specifically assessing its regulatory effects on Th2 cell responses and dendritic cells (DCs). Lower CC10 levels in asthma were observed and correlated with increased IgE and lymphocytes. Cc10 mice exhibited exacerbated allergic airway inflammation marked by increased inflammatory cell infiltration, Th2 cytokines, serum antigen-specific IgE levels, and airway hyperresponsiveness (AHR) in house dust mite (HDM)-induced models. Conversely, recombinant CC10 significantly attenuated these inflammatory responses. Intriguingly, CC10 did not directly inhibit Th cell activation but significantly downregulated the population of CD11bCD103 DCs subsets in lungs of asthmatic mice and modulated the immune activation functions of DCs through NF-κB signaling pathway. The mixed lymphocyte response assay revealed that DCs mediated the suppressive effect of CC10 on Th2 cell responses. Collectively, CC10 profoundly mitigates Th2-type allergic inflammation in asthma by modulating lung DC phenotype and functions, highlighting its therapeutic potential for inflammatory airway conditions and other related immunological disorders.
过敏性哮喘是一种复杂的炎症性疾病，主要由辅助性 T 细胞 2（Th2）淋巴细胞调控。抗炎蛋白 Clara 细胞 10-kDa（CC10），也称为分泌球蛋白家族 1A 成员 1（SCGB1A1），在调节呼吸疾病方面显示出潜力。然而，其在哮喘中的确切作用仍不清楚。本研究探讨了 CC10 抑制过敏性哮喘炎症的潜力，特别是评估其对 Th2 细胞反应和树突状细胞（DC）的调节作用。在哮喘中观察到 CC10 水平降低，并与 IgE 和淋巴细胞增加相关。Cc10 小鼠表现出加重的过敏性气道炎症，特征为炎症细胞浸润增加、Th2 细胞因子、血清抗原特异性 IgE 水平和气道高反应性（AHR）增加，在屋尘螨（HDM）诱导的模型中。相反，重组 CC10 显著减轻了这些炎症反应。有趣的是，CC10 并未直接抑制 Th 细胞激活，但显著下调了哮喘小鼠肺部 CD11bCD103 DC 亚群的数量，并通过 NF-κB 信号通路调节了 DC 的免疫激活功能。混合淋巴细胞反应试验表明，DC 介导了 CC10 对 Th2 细胞反应的抑制作用。总之，CC10 通过调节肺部 DC 表型和功能，显著减轻哮喘中的 Th2 型过敏性炎症，凸显其在炎症性气道疾病和其他相关免疫性疾病中的治疗潜力。
