Invariant natural killer T cells promote immunogenic maturation of lung dendritic cells in mouse models of asthma

被引:8
作者
He, Qing [1 ]
Liu, Linlin [1 ]
Yang, Qiaoyu [1 ]
Wang, Ailing [2 ]
Chen, Shuo [1 ]
Li, Ruiyun [1 ]
Huang, Yi [1 ]
Zhang, Guqin [3 ]
Ding, Xuhong [1 ]
Yu, Hongying [1 ]
Hu, Suping [1 ]
Nie, Hanxiang [1 ]
机构
[1] Wuhan Univ, Dept Resp Med, Renmin Hosp, 238 Jiefang Rd, Wuhan 430060, Hubei, Peoples R China
[2] Wuhan Univ, Sch Hlth Sci, Nursing Dept, Wuhan, Hubei, Peoples R China
[3] Wuhan Univ, Zhongnan Hosp, Dept Resp Med, Wuhan, Hubei, Peoples R China
基金
中国国家自然科学基金;
关键词
asthma; invariant natural killer cells; dendritic cells; Th2; responses; immunogenic maturation; ALLERGIC AIRWAY INFLAMMATION; NKT CELLS; IN-VIVO; GAMMA PRODUCTION; IMMUNITY; ANTIGEN; HYPERREACTIVITY; TOLERANCE; MACROPHAGES; ACTIVATION;
D O I
10.1152/ajplung.00340.2016
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Our previous study showed that invariant natural killer T (iNKT) cells might act as an adjuvant to promote Th2 inflammatory responses in an OVA-induced mouse model of allergic asthma, but the mechanism remains unknown. To clarify the underlying mechanism through which iNKT cells promote Th2 inflammatory responses, we investigated the modulatory influence of iNKT cells on phenotypic and functional maturation of lung dendritic cells (LDCs) using iNKT cell-knockout mice, specific iNKT cell activation, coculture experiments, and adoptive transfer of iNKT cells in mouse models of asthma. Our data showed that iNKT cell deficiency could downregulate surface maturation markers and proinflammatory cytokine secretion of LDCs from a mouse model of asthma. However, elevated activation of iNKT cells by alpha-galactosylceramide and adoptive transfer of iNKT cells could upregulate surface maturation markers and proinflammatory cytokine secretion of LDCs from mouse models of asthma. Meanwhile, iNKT cells significantly influenced the function of LDCs, markedly enhancing Th2 responses in vivo and in vitro. In addition, iNKT cell can induce LDCs expression of CD206 and RELM-alpha, reflecting alternative activation of LDCs in a mouse model of asthma. alpha-Galactosyl-ceramide treatment significantly enhanced expression of CD40L of lung iNKT cells from a mouse model of asthma, and the coculture experiment of LDCs with iNKT cells showed that the blockade of CD40L strongly suppressed surface maturation markers and proinflammatory cytokine production by LDCs. Our data suggest that iNKT cells can promote immunogenic maturation of LDCs to enhance Th2 responses in mouse models of asthma.
引用
收藏
页码:L973 / L990
页数:18
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