Zheng Rui, Chen Yang, Shi Jianbo, Wang Kai, Huang Xuekun, Sun Yueqi, Yang Qintai
Department of Otorhinolaryngology-Head and Neck Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Front Cell Dev Biol. 2020 Apr 3;8:207. doi: 10.3389/fcell.2020.00207. eCollection 2020.
Myeloid dendritic cells (DCs) in patients with allergic rhinitis (AR) express higher levels of IL-17RB, ST2, and TSLPR. However, their functional roles in DCs are much less clear. This study aimed to determine the combined effects of these three receptor signals on the T cell-polarizing function of DCs in AR patients.
Monocyte-derived DCs (mo-DCs) were generated and stimulated with Toll-like receptor (TLR) 1-9 ligands. Der.p1-induced mo-DCs were stimulated with different combinations of IL-25, IL-33, and TSLP to determine phenotypic characteristics and then co-cultured with CD4 T cells to assess Th2 cytokine production. Expression levels of IL-17RB, ST2, and TSLPR on myeloid DCs (mDCs) from peripheral blood of AR and healthy subjects were detected to confirm the association of these receptors with disease severity.
TLR ligands induced AR-derived mo-DCs to increase IL-17RB, ST2, and TSLPR expression by varying degrees; among these, Der.p1 was the strongest inducer. Der.p1-induced mo-DCs from AR showed increased OX40L expression. IL-25, IL-33, and TSLP (alone or in double combination) significantly increased OX40L expression on Der.p1-induced mo-DCs from AR, thereby increasing the production of IL-4, IL-5, and IL-13 in co-cultured CD4 T cells; triple combination further enhanced these effects. The percentage of IL-17RBST2TSLPR mDCs was increased in AR, higher in moderate to severe phase than in mild phase, and positively correlated with the percentages of IL-4, IL-5, and IL-13 T cells.
A combination of IL-17RB, ST2, and TSLPR signals amplified the Th2-polarizing function of DCs and was associated with disease severity in AR patients.
过敏性鼻炎（AR）患者的髓样树突状细胞（DCs）表达较高水平的白细胞介素17受体B（IL-17RB）、ST2和胸腺基质淋巴细胞生成素受体（TSLPR）。然而，它们在DCs中的功能作用尚不清楚。本研究旨在确定这三种受体信号对AR患者DCs的T细胞极化功能的联合作用。
生成单核细胞衍生的DCs（mo-DCs）并用Toll样受体（TLR）1-9配体进行刺激。用白细胞介素25（IL-25）、白细胞介素33（IL-33）和TSLP的不同组合刺激粉尘螨变应原1（Der.p1）诱导的mo-DCs，以确定其表型特征，然后与CD4 T细胞共培养以评估Th2细胞因子的产生。检测AR患者和健康受试者外周血髓样DCs（mDCs）上IL-17RB、ST2和TSLPR的表达水平，以确认这些受体与疾病严重程度的关联。
TLR配体诱导AR来源的mo-DCs不同程度地增加IL-17RB、ST2和TSLPR的表达；其中，Der.p1是最强的诱导剂。Der.p1诱导的AR来源的mo-DCs显示氧化40配体（OX40L）表达增加。IL-25、IL-33和TSLP（单独或联合）显著增加Der.p1诱导的AR来源的mo-DCs上的OX40L表达，从而增加共培养的CD4 T细胞中白细胞介素4（IL-4）、白细胞介素5（IL-5）和白细胞介素13（IL-13）的产生；三联组合进一步增强了这些作用。AR患者中IL-17RBST2TSLPR mDCs的百分比增加，中重度期高于轻度期，且与IL-4、IL-5和IL-13 T细胞的百分比呈正相关。
IL-17RB、ST2和TSLPR信号的组合放大了DCs向Th2极化的功能，并与AR患者的疾病严重程度相关。
