iNKT细胞介导的XCL1-XCR1轴通过募集CD103+树突细胞促进过敏性气道高反应性
2018/03/05
摘要
背景：据报道XCL1-XCR1轴在免疫稳态和炎症中起作用。然而，目前还不知道这个轴在过敏性哮喘中是否具有关键作用。
目的：在本研究中，我们研究了iNKT细胞介导的XCL1-XCR1轴调控过敏性哮喘。
方法：在XCL1或XCR1敲除（KO）小鼠中应用卵清蛋白（OVA）或屋尘螨（HDM）诱导哮喘。
结果：与OVA或HDM诱导的野生型（WT）哮喘小鼠相比，XCL1或XCR1 敲除小鼠肺中气道高反应性（AHR）减弱， CD103+树突细胞（DC）数目减少，Th2应答减弱。气管内应用重组XCL1或CD103+ DC过继转移到XCL1敲除小鼠后这些作用被逆转，但CD11b+ DC过继转移后无此作用。此外，iNKT细胞在体外和体内XCL1高表达。在鼻内α-半乳糖基神经酰胺刺激后，WT肺中的CD103+ DC数目增加，而XCL1 敲除小鼠中未增加。此外，OVA诱导的CD1d 敲除哮喘小鼠肺中，过继转移WT iNKT细胞增加了的AHR、CD103+ DC募集和Th2应答，而过继转移XCL1缺陷型iNKT细胞则没有次作用。在人体中，哮喘患者外周血单个核细胞来源的iNKT细胞的百分比和XCL1生产能力高于健康对照。
结论：这些数据表明，在变应性哮喘中iNKT细胞介导的XCL1-XCR1轴通过募集CD103+ DC入肺来促进AHR。
iNKT cell-mediated XCL1-XCR1 axis promotes allergic airway hyperresponsiveness by recruiting CD103+ dendritic cells.
Woo YD, Koh J, Kang HR, Kim HY, Chung DH.
Abstract
BACKGROUND:The XCL1-XCR1 axis has been reported to play a role in immune homeostasis and inflammation. However, it is not known whether this axis has a critical function in allergic asthma.
OBJECTIVE:In the present study, we explored that the iNKT cell-mediated XCL1-XCR1 axis regulated the allergic asthma.
METHODS:Ovalbumin (OVA) or house dust mite (HDM)-induced asthma was developed in XCL1 or XCR1 knockout (KO) mice.
RESULTS:XCL1 or XCR1 KO mice showed attenuation in airway hyperresponsiveness (AHR), numbers of CD103+ dendritic cells (DCs), and Th2 responses in the lungs compared with wild-type (WT) mice during OVA or HDM-induced asthma. These effects were reversed by intratracheal administration of recombinant XCL1 or adoptive transfer of CD103+ DCs, but not CD11b+ DCs into XCL1 KO mice. Moreover, iNKTcells highly expressed XCL1 in vitro and in vivo. Upon intranasal α-galactosyl ceramide challenge, CD103+ DC numbers in the lungs were increased in WT, but not XCL1 KO mice. Furthermore, adoptive transfer of WT iNKT cells increased AHR, CD103+ DC recruitment, and Th2 responses in the lungs of CD1d KO mice during OVA-induced asthma, whereas that of XCL1-deficient iNKT cells did not. In human, the percentages and XCL1 production capacity of iNKT cells from peripheral blood mononuclear cells were higher in patients with asthma than healthy control.
CONCLUSION:These data demonstrate that the iNKT cell-mediated XCL1-XCR1 axis promotes AHR by recruiting CD103+ DCs into the lung in allergic asthma.
背景：据报道XCL1-XCR1轴在免疫稳态和炎症中起作用。然而，目前还不知道这个轴在过敏性哮喘中是否具有关键作用。
目的：在本研究中，我们研究了iNKT细胞介导的XCL1-XCR1轴调控过敏性哮喘。
方法：在XCL1或XCR1敲除（KO）小鼠中应用卵清蛋白（OVA）或屋尘螨（HDM）诱导哮喘。
结果：与OVA或HDM诱导的野生型（WT）哮喘小鼠相比，XCL1或XCR1 敲除小鼠肺中气道高反应性（AHR）减弱， CD103+树突细胞（DC）数目减少，Th2应答减弱。气管内应用重组XCL1或CD103+ DC过继转移到XCL1敲除小鼠后这些作用被逆转，但CD11b+ DC过继转移后无此作用。此外，iNKT细胞在体外和体内XCL1高表达。在鼻内α-半乳糖基神经酰胺刺激后，WT肺中的CD103+ DC数目增加，而XCL1 敲除小鼠中未增加。此外，OVA诱导的CD1d 敲除哮喘小鼠肺中，过继转移WT iNKT细胞增加了的AHR、CD103+ DC募集和Th2应答，而过继转移XCL1缺陷型iNKT细胞则没有次作用。在人体中，哮喘患者外周血单个核细胞来源的iNKT细胞的百分比和XCL1生产能力高于健康对照。
结论：这些数据表明，在变应性哮喘中iNKT细胞介导的XCL1-XCR1轴通过募集CD103+ DC入肺来促进AHR。
(中日友好医院呼吸与危重症医学科 顾宪民 摘译 林江涛 审校)
(J Allergy Clin Immunol. 2018 Feb 20. pii: S0091-6749(18)30283-5)
(J Allergy Clin Immunol. 2018 Feb 20. pii: S0091-6749(18)30283-5)
iNKT cell-mediated XCL1-XCR1 axis promotes allergic airway hyperresponsiveness by recruiting CD103+ dendritic cells.
Woo YD, Koh J, Kang HR, Kim HY, Chung DH.
Abstract
BACKGROUND:The XCL1-XCR1 axis has been reported to play a role in immune homeostasis and inflammation. However, it is not known whether this axis has a critical function in allergic asthma.
OBJECTIVE:In the present study, we explored that the iNKT cell-mediated XCL1-XCR1 axis regulated the allergic asthma.
METHODS:Ovalbumin (OVA) or house dust mite (HDM)-induced asthma was developed in XCL1 or XCR1 knockout (KO) mice.
RESULTS:XCL1 or XCR1 KO mice showed attenuation in airway hyperresponsiveness (AHR), numbers of CD103+ dendritic cells (DCs), and Th2 responses in the lungs compared with wild-type (WT) mice during OVA or HDM-induced asthma. These effects were reversed by intratracheal administration of recombinant XCL1 or adoptive transfer of CD103+ DCs, but not CD11b+ DCs into XCL1 KO mice. Moreover, iNKTcells highly expressed XCL1 in vitro and in vivo. Upon intranasal α-galactosyl ceramide challenge, CD103+ DC numbers in the lungs were increased in WT, but not XCL1 KO mice. Furthermore, adoptive transfer of WT iNKT cells increased AHR, CD103+ DC recruitment, and Th2 responses in the lungs of CD1d KO mice during OVA-induced asthma, whereas that of XCL1-deficient iNKT cells did not. In human, the percentages and XCL1 production capacity of iNKT cells from peripheral blood mononuclear cells were higher in patients with asthma than healthy control.
CONCLUSION:These data demonstrate that the iNKT cell-mediated XCL1-XCR1 axis promotes AHR by recruiting CD103+ DCs into the lung in allergic asthma.
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低密度脂蛋白受体相关蛋白1通过抑制树突状细胞介导的适应性免疫应答来减弱屋尘螨诱导的嗜酸性气道炎症
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