BACKGROUND Group 2 innate lymphoid cells (ILC2s) were reported to serve a critical role in allergic diseases. Myeloid dendritic cells (mDCs) and plasmacytoid DCs (pDCs) play significant roles in allergic immune response. However, effects of DCs on ILC2s in allergic diseases, especially for patients with allergic rhinitis (AR), remain unclear. OBJECTIVE We sought to address the roles of mDCs and pDCs in regulating ILC2 function in AR. METHODS mDCs and pDCs were cocultured with human PBMCs isolated from patients with AR or ILC2s to measure soluble or intracellular TH2 cytokines, transcription factors, signaling pathways in ILC2s, and the following mechanisms were further investigated. The levels of peripheral IL-33+mDCs, pDCs, and ILC2s were studied in patients under an inhaled allergen challenge. RESULTS We confirmed the presence of ILC2s, mDCs, and pDCs in the nasal mucosa of patients with AR. Both allogenic and autologous mDCs were found to activate ILC2s from patients with AR to produce TH2 cytokines, and increase the levels of GATA-3 and signal transducer and activator of transcription signaling pathways, in which IL-33-producing mDCs exerted the major role by binding on ST2 on ILC2s. We further identified high levels of IL-33+mDCs and ILC2s in patients with AR under antigen challenge. Activated pDCs inhibited the cytokine production of ILC2s isolated from patients with AR by secretion of IL-6. CONCLUSIONS mDCs promote ILC2 function by the IL-33/ST2 pathway, and activation of pDCs suppresses ILC2 function through IL-6 in patients with AR. Our findings provide new understanding of the interplay between DCs and ILC2s in allergic diseases.

中文翻译：

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变应性鼻炎患者骨髓和浆细胞样树突状细胞对ILC2s的影响。

背景技术据报道，第2组先天性淋巴样细胞（ILC2）在过敏性疾病中起关键作用。髓样树突状细胞（mDCs）和浆细胞样DC（pDCs）在过敏性免疫反应中起重要作用。但是，DC对变应性疾病中ILC2s的影响，特别是对过敏性鼻炎（AR）患者的影响仍不清楚。目的我们试图解决mDC和pDC在调节AR中ILC2功能中的作用。方法将mDCs和pDCs与AR或ILC2s患者分离的人PBMCs共培养，以测量可溶性或细胞内TH2细胞因子，转录因子，ILC2s中的信号通路，并进一步研究以下机制。在吸入性过敏原激发下的患者中研究了外周血IL-33 + mDCs，pDCs和ILC2s的水平。结果我们确认了ILC2，mDC，AR患者鼻黏膜中的pDC和pDC。发现同种异体和自体mDC均能激活AR患者的ILC2，从而产生TH2细胞因子，并增加GATA-3和信号转导子及转录信号通路的激活子的水平，其中产生IL-33的mDC发挥了主要作用。在ILC2上的ST2上绑定。我们进一步在抗原挑战下的AR患者中发现了高水平的IL-33 + mDCs和ILC2s。激活的pDC通过分泌IL-6抑制从AR患者中分离出的ILC2的细胞因子产生。结论mDCs通过IL-33 / ST2途径促进ILC2功能，而pDCs的激活通过IL-6抑制AR患者的ILC2功能。我们的发现为过敏性疾病中DC和ILC2之间的相互作用提供了新的认识。