T helper cell IL-4 drives intestinal Th2 priming to oral peanut antigen, under the control of OX40L and independent of innate-like lymphocytes
T helper cell IL-4 drives intestinal Th2 priming to oral peanut antigen, under the control of OX40L and independent of innate-like lymphocytes
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DOI：
10.1038/mi.2014.29
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发表时间：
2014-11-01
影响因子：
8
通讯作者：
Jordana, M.
中科院分区：
文献类型：
--
作者：
Chu, D. K.;Mohammed-Ali, Z.;Jordana, M.
食物过敏中的肠道辅助性T细胞2型（Th 2）免疫导致IgG 1和IgE产生，抗原再暴露诱发过敏反应，如过敏反应和嗜酸性粒细胞炎症。虽然白细胞介素-4（IL-4）是过敏性致敏所必需的，但体内Th 2免疫启动过程中IL-4的来源和控制仍不清楚。非肠道和非食物过敏系统已经表明，天然的免疫球蛋白样T（NKT）或γ δ T细胞先天性淋巴细胞可以提供诱导Th 2极化所需的IL-4。第2组先天性淋巴样细胞（ILC）是一种新的IL-4活性细胞群，但它们对启动适应性Th 2免疫的作用尚不清楚。也有IL-4非依赖性Th 2应答的报道。在这里，我们表明，IL-4依赖花生过敏性Th 2反应是完全完整的NKT缺陷，γ δ T缺陷或ILC缺陷的小鼠，包括抗原特异性IgG 1/ IgE的生产，过敏反应，和细胞因子的生产。相反，仅来自CD 4（+）Th细胞的IL-4诱导完全的Th 2免疫。此外，体内IL-4的CD 4（+）Th细胞产生依赖于OX 40 L，OX 40 L是肠过敏引发所需的树突状细胞（DC）上的共刺激分子。然而，Th 2细胞和ILC都协调了IL-13依赖性嗜酸性粒细胞炎症。因此，肠道Th 2启动是由自分泌/旁分泌作用的CD 4（+）Th细胞内在IL-4程序启动的，该程序由DC OX 40 L控制，而不是由NKT、γ δ T或ILC细胞控制。
Intestinal T helper type 2 (Th2) immunity in food allergy results in IgG1 and IgE production, and antigen re-exposure elicits responses such as anaphylaxis and eosinophilic inflammation. Although interleukin-4 (IL-4) is critically required for allergic sensitization, the source and control of IL-4 during the initiation of Th2 immunity in vivo remains unclear. Nonintestinal and non-food allergy systems have suggested that natural killer-like T (NKT) or gamma delta T-cell innate lymphocytes can supply the IL-4 required to induce Th2 polarization. Group 2 innate lymphoid cells (ILCs) are a novel IL-4-competent population, but their contribution to initiating adaptive Th2 immunity is unclear. There are also reports of IL-4independent Th2 responses. Here, we show that IL-4-dependent peanut allergic Th2 responses are completely intact in NKT-deficient, gamma delta T-deficient or ILC-deficient mice, including antigen-specific IgG1/ IgE production, anaphylaxis, and cytokine production. Instead, IL-4 solely from CD4(+) Th cells induces full Th2 immunity. Further, CD4(+) Th cell production of IL-4 in vivo is dependent on OX40L, a costimulatory molecule on dendritic cells (DCs) required for intestinal allergic priming. However, both Th2 cells and ILCs orchestrated IL-13-dependent eosinophilic inflammation. Thus, intestinal Th2 priming is initiated by an autocrine/paracrine acting CD4(+) Th cell-intrinsic IL-4 program that is controlled by DC OX40L, and not by NKT, gamma delta T, or ILC cells.