Plasmacytoid dendritic cells (pDCs) regulate immunity and promote tolerance in asthma. Notch signalling is a highly conserved pathway that regulates the immune response; however, its role in pDC-mediated asthmatic airway inflammation is unclear. This study clarified the effects of Notch signalling on pDC-mediated airway inflammation using murine models of ovalbumin-sensitized allergic asthma. RBP-J-deficient pDCs (RBP-J-/- pDCs) were co-cultured with naïve CD4+ T cells and supernatants and T cell subtypes were analysed. RBP-J-/- pDCs were intranasally transferred to the airways of ovalbumin-sensitized recipient mice. Lung samples of all mice were subjected to tests for histopathology, cytokine profile of bronchoalveolar lavage fluid, airway hyperactivity and expression of T helper type 1 (Th1)/Th2 cells, regulatory T cells and type 2 innate lymphoid cells (ILC2s). The results showed that pDCs with and without RBP-J deficiency significantly differed in expression levels of cluster of differentiation 83 (CD83), but not CD80, CD86 and major histocompatibility complex class II. Co-culturing pDCs with naïve T cells revealed a poorer immunosuppressive effect of RBP-J-/- pDCs. This may be attributed to the lower expression levels of inducible co-stimulator ligand and lower production of interleukin 10 in RBP-J-/- pDCs than in control pDCs, which impeded T cell activation and Treg suppression. RBP-J-/- pDCs were associated with high ILC2 expression and severe Th2 immune responses and airway inflammation. Therefore, Notch signalling is critical for pDC-dependent immunoregulation, and RBP-J deficiency reduces pDC-based immunosuppression via T cell activation and Th cell differentiation. Thus, this pathway may be a therapeutic target for pDC-based anti-asthma immunotherapy.

中文翻译：

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Notch途径的破坏通过通过调节浆细胞样树突状细胞来抑制调节性T细胞分化而加剧了气道炎症。

浆细胞样树突状细胞（pDC）调节免疫力并增强哮喘的耐受性。Notch信号传导是调节免疫反应的高度保守的途径。然而，其在pDC介导的哮喘气道炎症中的作用尚不清楚。这项研究使用卵清蛋白敏感的过敏性哮喘小鼠模型阐明了Notch信号对pDC介导的气道炎症的影响。将缺乏RBP-J的pDC（RBP-J-/-pDC）与原始CD4 + T细胞共培养，并分析上清液和T细胞亚型。RBP-J-/-pDCs经鼻内转移到卵清蛋白敏感的受体小鼠的气道中。对所有小鼠的肺样品进行组织病理学检查，支气管肺泡灌洗液的细胞因子谱，气道亢进以及T辅助1型（Th1）/ Th2细胞的表达，调节性T细胞和2型先天淋巴样细胞（ILC2s）。结果显示，具有和不具有RBP-J缺乏的pDC在分化簇83（CD83）的表达水平上有显着差异，而CD80，CD86和主要组织相容性复合物II类则没有差异。将pDC与幼稚T细胞共培养显示RBP-J-/-pDC的免疫抑制作用较弱。这可能归因于与对照pDC相比，RBP-J-/-pDC中诱导型共刺激配体的较低表达水平和白介素10的产生较低，这阻碍了T细胞活化和Treg抑制。RBP-J-/-pDC与高ILC2表达，严重的Th2免疫反应和气道炎症相关。因此，Notch信号对于pDC依赖性免疫调节至关重要，RBP-J缺乏可通过T细胞活化和Th细胞分化降低基于pDC的免疫抑制。因此，该途径可能是基于pDC的抗哮喘免疫疗法的治疗目标。