Group 2 innate lymphoid cells and CD4+ T cells cooperate to mediate type 2 immune response in mice.
Group 2 innate lymphoid cells and CD4+ T cells cooperate to mediate type 2 immune response in mice.
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作者：
Drake LY;Iijima K;Kita H
先天淋巴细胞（ILC）通过产生各种细胞因子和生长因子，在先天免疫和组织重塑中发挥重要作用。最近显示，即使没有适应性免疫，第 2 组 ILC (ILC2) 也能介导哮喘的免疫病理学。然而，人们对 ILC2 与其他免疫细胞之间可能的相互作用知之甚少。我们试图研究 ILC2 调节 T 细胞效应功能的能力。我们从幼鼠的肺部分离出 ILC2。我们在体外培养了带有 ILC2 的 CD4+ T 细胞，并检查了这些细胞类型的功能。通过使用阻断抗体和从细胞因子缺陷小鼠中分离的细胞来研究其机制。在体内研究中，我们将 ILC2 和 CD4+ T 细胞过继转移到 Il7ra−/− 小鼠中，随后将小鼠暴露于卵清蛋白和半胱氨酸蛋白酶中。肺 ILC2 增强 CD4+ T 细胞增殖并促进体外 2 型细胞因子的产生。 ILC2与CD4+T细胞的相互作用涉及共刺激分子OX40L和细胞因子IL-4，其主要来源于ILC2。将 ILC2 和 CD4+ T 细胞群（而不是单独的每个群）过继转移到 Il7ra−/− 小鼠中，导致诱导强烈的抗原特异性 2 型细胞因子反应和气道炎症。肺 ILC2 除了在先天免疫中的既定作用外，还具有促进适应性免疫的功能。在考虑哮喘和其他过敏性气道疾病的病理生理学时，需要考虑 ILC2 的这种新功能。
Innate lymphoid cells (ILCs) play important roles in innate immunity and tissue remodeling via production of various cytokines and growth factors. Group 2 ILCs (ILC2s) were recently shown to mediate the immune pathology of asthma even without adaptive immunity. However, little is known about possible interactions between ILC2s and other immune cells. We sought to investigate the capacity of ILC2s to regulate effector functions of T cells. We isolated ILC2s from the lungs of naïve mice. We cultured CD4+ T cells with ILC2s in vitro and examined the functions of these cell types. The mechanisms were investigated by using blocking antibodies and cells isolated from cytokine-deficient mice. For the in vivo study, we adoptively transferred ILC2s and CD4+ T cells into Il7ra−/− mice and subsequently exposed the mice to ovalbumin and a cysteine protease. Lung ILC2s enhanced CD4+ T cell proliferation and promoted production of type 2 cytokines in vitro. The interaction between ILC2s and CD4+ T cells involved costimulatory molecule OX40L and cytokine IL-4, which was mainly derived from ILC2s. Adoptive transfer of both ILC2 and CD4+ T cell populations, but not each population alone, into Il7ra−/− mice resulted in induction of a robust antigen-specific type 2 cytokine response and airway inflammation. Lung ILC2s function to promote adaptive immunity in addition to their established roles in innate immunity. This novel function of ILC2s needs to be taken into account when considering the pathophysiology of asthma and other allergic airway diseases.
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DOI：
10.4049/jimmunol.1101632
发表时间：
2012-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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作者：
Doherty TA;Khorram N;Sugimoto K;Sheppard D;Rosenthal P;Cho JY;Pham A;Miller M;Croft M;Broide DH
通讯作者：
Broide DH
DOI：
10.1073/pnas.1003988107
发表时间：
2010-06-22
影响因子：
11.1
作者：
Price, April E.;Liang, Hong-Erh;Locksley, Richard M.
通讯作者：
Locksley, Richard M.
影响因子：
32.4
作者：
Halim, Timotheus Y. F.;Krauss, Ramona H.;Takei, Fumio
通讯作者：
Takei, Fumio
影响因子：
64.8
作者：
通讯作者：
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影响因子：
64.8
作者：
通讯作者：
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