IL-4 enhances IFN-λ1 (IL-29) production by plasmacytoid DCs via monocyte secretion of IL-1Ra
IL-4 enhances IFN-λ1 (IL-29) production by plasmacytoid DCs via monocyte secretion of IL-1Ra
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DOI：
10.1182/blood-2009-09-246157
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发表时间：
2010-05-27
期刊：
影响因子：
20.3
通讯作者：
Gallagher, Grant
中科院分区：
文献类型：
--
作者：
Megjugorac, Nicholas J.;Gallagher, Grant E.;Gallagher, Grant
III型干扰素（IFN）家族由人体内的3种分子组成：IFN-λ 1（白细胞介素-29 [IL-29]）、IFN-λ 2（IL-28 A）和IFN-λ 3（IL-28 B），每种分子都通过相同的受体复合物发出信号。浆细胞样树突状细胞（pDC）是外周血淋巴细胞中主要的IFN-λ产生者。最近，研究表明，IFN-lambda 1通过拮抗IL-4对CD 4（+）T细胞的作用并抑制Th 2相关细胞因子的产生，对辅助性T细胞2（Th 2）反应产生强大的抑制作用。在这里，我们问是否Th 2细胞因子发挥相互控制IFN-λ的生产。在刺激人外周淋巴细胞的过程中，IL-4处理显著提高了IFN-λ 1的转录和分泌。然而，pDC不直接响应于IL-4。使用消耗和重建实验，我们表明，IL-4-响应单核细胞是一个中介细胞，响应IL-4通过提高其分泌的IL-1受体拮抗剂（IL-Ra）;这种IL-1 Ra作用于pDC，以提高其IFN-λ 1输出。因此，我们的实验揭示了一种新的机制，调节IFN-λ 1的生产和pDC的功能，并建议扩大免疫调节作用的Th 2相关的细胞因子。（血。2010; 115（21）：4185-4190）
The type-III interferon (IFN) family is composed of 3 molecules in humans: IFN-lambda 1 (interleukin-29 [IL-29]), IFN-lambda 2 (IL-28A), and IFN-lambda 3 (IL-28B), each of which signals through the same receptor complex. Plasmacytoid dendritic cells (pDCs) are major IFN-lambda producers among peripheral lymphocytes. Recently, it has been shown that IFN-lambda 1 exerts a powerful inhibitory effect over the T-helper 2 (Th2) response by antagonizing the effect of IL-4 on CD4(+) T cells and inhibiting the production of Th2-associated cytokines. Here, we asked whether Th2 cytokines exert reciprocal control over IFN-lambda production. IL-4 treatment during stimulation of human peripheral lymphocytes significantly elevated IFN-lambda 1 transcription and secretion. However, pDCs were not directly responsive to IL-4. Using depletion and reconstitution experiments, we showed that IL-4-responsive monocytes are an intermediary cell, responding to IL-4 by elevating their secretion of IL-1 receptor antagonist (IL-Ra); this IL-1Ra acts on pDCs to elevate their IFN-lambda 1 output. Thus, our experiments revealed a novel mechanism for regulation of both IFN-lambda 1 production and pDC function, and suggests an expanded immunomodulatory role for Th2-associated cytokines. (Blood. 2010; 115(21): 4185-4190)