Mal-deficiency impairs the tolerogenicity of dendritic cell of patients with allergic rhinitis
Mal-deficiency impairs the tolerogenicity of dendritic cell of patients with allergic rhinitis
复制标题
缺陷会损害过敏性鼻炎患者树突状细胞的耐受性
DOI：
10.1016/j.cellimm.2019.103930
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发表时间：
2019-10-01
影响因子：
4.3
通讯作者：
Yang, Ping-Chang
中科院分区：
文献类型：
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作者：
Shao, Jian-Bo;Yang, Gui;Yang, Ping-Chang
耐受性树突状细胞功能障碍与免疫性疾病的发病机制有关。微生物刺激是维持免疫功能所必需的。本研究旨在阐明Mal信号在维持DEC205(+) DC （decDC）免疫耐受原功能中的作用。本研究收集变应性鼻炎（AR）患者和健康对照（HC）受试者的外周dc，以评估decdc的功能状态。我们建立了AR小鼠模型来研究Mal信号在维持decdc功能中的作用。我们观察到AR decdc（来自AR患者的decdc）不能诱导1型调节性T细胞（Tr1细胞）。与HC decdc相比，AR decdc表达IL-10较少。IL-10 mRNA在AR decdc中自发衰减。TDP43可保护IL-10 mRNA免于衰变。AR decdc表达Mal水平低于HC decdc。Mal缺失导致HC decdc中IL-10 mRNA的衰减。AR decdc中Mal的重建恢复了诱导Tr1细胞的能力，并减弱了小鼠的实验性AR。综上所述，Mal在维持decDC的免疫耐受功能中起着至关重要的作用。Mal信号的缺失或不足会损害decDC的耐受性。AR decdc中Mal的重建可以恢复免疫耐受能力，这可能在AR和其他过敏性疾病的治疗中具有转化潜力。
The tolerogenic dendritic cell dysfunction is associated with the pathogenesis of immune diseases. Microbial stimulus is required in the maintenance of immune functions. This study aims to elucidate the role of Mal signal in the maintenance of DEC205(+) DC (decDC) immune tolerogenic function. In this study, peripheral DCs were collected from allergic rhinitis (AR) patients and healthy control (HC) subjects to assess the functional status of decDCs. An AR murine model was developed to WA the role of Mal signals in the maintenance of decDCs' functions. We observed that AR decDCs (decDCs obtained from AR patients) were incompetent in the induction of type 1 regulatory T cells (Tr1 cells). AR decDCs expressed less IL-10 than that in HC decDCs. IL-10 mRNA decayed spontaneously in AR decDCs. Tat-activating regulatory DNA-binding protein-43 (TDP43) protected IL-10 mRNA from decay. AR decDCs expressed lower levels of Mal than that in HC decDCs. Mal depletion resulted in IL-10 mRNA decay in HC decDCs. Reconstitution of Mal in AR decDCs restored the capacity of inducing Tr1 cells and attenuated experimental AR in mice. In conclusion, Mal plays a critical role in the maintenance of decDC's immune tolerogenic function. The absence or insufficient Mal signal impairs decDC's tolerogenic property. Reconstitution of Mal in AR decDCs can restore the immune tolerogenic capacity, which may have translational potential in the treatment of AR and other allergic diseases.