期刊
SCANDINAVIAN JOURNAL OF IMMUNOLOGY
卷 91, 期 5, 页码 -出版社
WILEY
DOI: 10.1111/sji.12865
关键词
asthma; ICOS-L; ILC2; interleukin-10; plasmacytoid dendritic cell; Th2
类别
资金
- National Natural Science Foundation of China [No. 81200018] Funding Source: Medline
- Natural Science Foundation of Shaanxi Province [No. 2014JQ4163] Funding Source: Medline
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 naive 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 naive 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.
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