PGI2 Controls Pulmonary NK Cells That Prevent Airway Sensitization to House Dust Mite Allergen.
PGI2 Controls Pulmonary NK Cells That Prevent Airway Sensitization to House Dust Mite Allergen.
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DOI：
10.4049/jimmunol.1600275
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发表时间：
2017-01-01
期刊：
影响因子：
--
通讯作者：
Roberts K
中科院分区：
文献类型：
--
作者：
Simons B;Ferrini ME;Carvalho S;Bassett DJ;Jaffar Z;Roberts K
在过敏性哮喘中，吸入空气中的过敏原，如屋尘螨（HDM），有效地激活肺粘膜中的先天性和适应性免疫。为了确定类花生酸PGI 2及其受体IP在过敏性气道致敏过程中的作用，将缺乏功能性IP受体（IP-/-）的小鼠的HDM反应与野生型（WT）小鼠进行了比较。令人惊讶的是，与WT动物相比，IP−/−小鼠产生IFN-γ的肺CD 3 −NK1.1+ Ly 49 b + NK细胞数量增加，与表达IL-33 R α和IL-13的2型先天淋巴细胞（ILC 2）数量呈负相关。这种现象与IP−/−小鼠气道中CX 3CL 1水平升高有关，用CX 3CL 1中和抗体治疗可减少肺NK细胞产生IFN-γ。值得注意的是，IP−/−小鼠对HDM攻击的反应低于WT小鼠，因为鼻内滴注过敏原诱导气道嗜酸性粒细胞、CD 4+淋巴细胞浸润和粘液产生水平显著降低，以及CCL 2趋化因子和Th 2细胞因子水平降低。NK细胞负责这种减弱的反应，因为IP−/−小鼠中NK1.1+细胞的耗竭恢复了HDM诱导的肺部炎症和ILC 2数量，而将CD 3 −NK1.1+ NK细胞转移到WT宿主的气道中抑制了炎症反应。总的来说，这些数据证明了PGI 2在调节肺组织中驻留的NK细胞的数量和性质方面的迄今未知的作用，并揭示了NK细胞在限制肺组织ILC 2和预防对吸入的HDM过敏原的过敏性炎症反应方面的作用。
In allergic asthma, inhalation of airborne allergens such as house dust mite (HDM) effectively activates both innate and adaptive immunity in the lung mucosa. To determine the role of the eicosanoid PGI2 and its receptor IP during allergic airway sensitization, HDM responses in mice lacking a functional IP receptor (IP−/−) were compared to wild type (WT) mice. Surprisingly, IP−/− mice had increased numbers of pulmonary CD3−NK1.1+Ly49b+ NK cells producing IFN-γ that was inversely associated with the number of type 2 innate lymphoid cells (ILC2s) expressing IL-33Rα and IL-13 compared to WT animals. This phenomenon was associated with elevated CX3CL1 levels in the airways of IP−/− mice and treatment with a neutralizing antibody to CX3CL1 reduced IFN-γ production by the lung NK cells. Remarkably, IP−/− mice were less responsive to HDM challenge than WT counterparts since intranasal instillation of the allergen induced markedly reduced levels of airway eosinophils, CD4+ lymphocyte infiltration and mucus production, as well as depressed levels of CCL2 chemokine and Th2 cytokines. NK cells were responsible for such attenuated responses since depletion of NK1.1+ cells in IP−/− mice restored both the HDM-induced lung inflammation and ILC2 numbers, while transfer of CD3−NK1.1+ NK cells into the airways of WT hosts suppressed the inflammatory response. Collectively, these data demonstrate a hitherto unknown role for PGI2 in regulating the number and properties of NK cells resident in lung tissue and reveal a role for NK cells in limiting lung tissue ILC2s and preventing allergic inflammatory responses to inhaled HDM allergen.
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DOI：
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影响因子：
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作者：
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DOI：
10.4049/jimmunol.1004007
发表时间：
2011-06-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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Haworth O;Cernadas M;Levy BD
通讯作者：
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