The T helper type 2 response to cysteine proteases requires dendritic cell-basophil cooperation via ROS-mediated signaling.
The T helper type 2 response to cysteine proteases requires dendritic cell-basophil cooperation via ROS-mediated signaling.
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启动辅助性T细胞2型（TH 2）反应的机制知之甚少。在这里，我们表明，半胱氨酸蛋白酶诱导的TH 2反应发生通过迁移真皮树突状细胞（DC）和嗜碱性粒细胞之间的“合作”白细胞介素4（IL-4）阳性。木瓜蛋白酶加抗原皮下免疫诱导淋巴结DC和真皮DC和皮肤上皮细胞中的活性氧（ROS）。ROS通过诱导氧化脂质，触发Toll样受体4（TLR 4）和衔接蛋白TRIF介导的上皮细胞诱导胸腺基质淋巴细胞生成素（TSLP），通过抑制淋巴结DC中TH 1诱导分子IL-12和CD 70的产生，协调TH 2应答;以及通过诱导DC衍生的趋化因子CCL 7，其介导IL-4+嗜碱性粒细胞向淋巴结的募集。因此，TH 2对半胱氨酸蛋白酶的反应需要DC-嗜碱性粒细胞通过ROS介导的信号传导进行合作。
The mechanisms that initiate T helper type 2 (TH2) responses are poorly understood. Here we demonstrate that cysteine protease–induced TH2 responses occur via ‘cooperation’ between migratory dermal dendritic cells (DCs) and basophils positive for interleukin 4 (IL-4). Subcutaneous immunization with papain plus antigen induced reactive oxygen species (ROS) in lymph node DCs and in dermal DCs and epithelial cells of the skin. ROS orchestrated TH2 responses by inducing oxidized lipids that triggered the induction of thymic stromal lymphopoietin (TSLP) by epithelial cells mediated by Toll-like receptor 4 (TLR4) and the adaptor protein TRIF; by suppressing production of the TH1-inducing molecules IL-12 and CD70 in lymph node DCs; and by inducing the DC-derived chemokine CCL7, which mediated recruitment of IL-4+ basophils to the lymph node. Thus, the TH2 response to cysteine proteases requires DC-basophil cooperation via ROS-mediated signaling.