Department of Otolaryngology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Pediatr Allergy Immunol. 2018 Sep;29(6):622-629. doi: 10.1111/pai.12926. Epub 2018 Jun 19.
Recent studies suggest that T helper 17 (Th17) cell subset, a distinct pro-inflammatory CD4 + T cell lineage, may play an important role in the pathophysiology of allergic rhinitis (AR). However, the regulation of Th17 response in allergic disease is not well characterized.
Thirty AR and 30 healthy children were enrolled. Serum leptin and OPN levels were measured, and their correlation with IL-17 expression was analyzed using enzyme-linked immunosorbent assay (ELISA). Th17 cell differentiation and cytokine production in peripheral blood mononuclear cell (PBMCs) stimulated by leptin and OPN and related inhibitors were analyzed by ELISA. AR mice models were also established to verify the effect of leptin and OPN on Th17 cell regulation. Immunoprecipitation was performed to explore the interaction between OPN and leptin in Th17 cells.
Our results showed that elevated serum leptin and OPN in AR children were correlated with serum IL-17 level (r = .53, P < .01). The recombinant leptin and OPN enhanced Th17 responses from PBMCs synergistically through nuclear factor κB (NF-κB), mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK) pathway and β3 integrin receptor. The AR mice showed as more severe Th17 responses and symptoms compared with control mice. Immunoprecipitation showed that OPN and leptin may interact with each other directly, and this process may be mediated by β3 integrin.
Our data provide evidence that upregulation of leptin and OPN promotes Th17 responses in AR, and this process may be achieved through NF-κB, MAPK, and JNK pathway and β3 integrin.
最近的研究表明，辅助性 T 细胞 17（Th17）亚群，一种独特的促炎 CD4+T 细胞谱系，可能在变应性鼻炎（AR）的病理生理学中发挥重要作用。然而，过敏疾病中 Th17 反应的调节尚不清楚。
纳入 30 名 AR 患儿和 30 名健康儿童。采用酶联免疫吸附试验（ELISA）检测血清瘦素和 OPN 水平，并分析其与 IL-17 表达的相关性。采用 ELISA 分析瘦素和 OPN 及其相关抑制剂刺激外周血单个核细胞（PBMCs）中 Th17 细胞分化和细胞因子产生的情况。还建立了 AR 小鼠模型，以验证瘦素和 OPN 对 Th17 细胞调节的影响。采用免疫沉淀法探索 OPN 与 Th17 细胞中瘦素的相互作用。
我们的结果表明，AR 患儿血清瘦素和 OPN 升高与血清 IL-17 水平相关（r=0.53，P<0.01）。重组瘦素和 OPN 通过核因子 κB（NF-κB）、丝裂原活化蛋白激酶（MAPK）和 c-Jun N 端激酶（JNK）途径以及β3 整合素受体协同增强 PBMCs 中的 Th17 反应。与对照小鼠相比，AR 小鼠表现出更严重的 Th17 反应和症状。免疫沉淀表明 OPN 和瘦素可能直接相互作用，这一过程可能通过β3 整合素介导。
我们的数据提供了证据，表明上调的瘦素和 OPN 促进 AR 中的 Th17 反应，这一过程可能通过 NF-κB、MAPK 和 JNK 途径以及β3 整合素实现。
