Luo Xi, Wen Yanhui, Qiu Xiangqian, Zhou Lifeng, Zeng Qingxiang, Liu Wenlong
Department of Otolaryngology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, China.
Department of Otolaryngology, The First Affiliated Hospital, Jinan University, Guangzhou 510630, China.
Biomedicines. 2025 May 21;13(5):1263. doi: 10.3390/biomedicines13051263.
Allergic rhinitis (AR) is triggered by immunoglobulin E (IgE)-mediated immune responses to airborne allergens. Recent studies highlight the pivotal role of T follicular helper 2 (Tfh2) cells in IgE production. Interleukin-37 (IL-37) has emerged as an intrinsic modulator of innate immunity and inflammatory processes. We aimed to investigate the regulatory effect of IL-37 on Tfh2 cells in the pathogenesis of AR. Blood samples were collected from AR patients and controls. The IL-37 levels and the frequency of Tfh2 cells were detected by enzyme-linked immunosorbent assay (ELISA) and flow cytometry, respectively. The isolated Tfh2 cells were cultured or cocultured with naive B cells. The regulatory effects of IL-37 on Tfh2/B cells were assessed using ELISA, quantitative real-time polymerase chain reaction (qRT-PCR). Mouse models of ovalbumin (OVA)-induced AR were established to explore the effect of IL-37 in vivo. IL-37 suppressed the production of IL-4 and IL-21 by Tfh2 cells and downregulated C-X-C chemokine receptor type 5 (CXCR5) and B-cell lymphoma 6 protein (Bcl6) mRNA expression while upregulating B lymphocyte-induced maturation protein 1 (Blimp1) and signal transducers and activators of transduction5 (STAT5) mRNA. IL-37 decreased IgE production by B cells significantly, and the addition of anti-IL-18 receptor α alleviated this effect. In mouse models, IL-37 reduced nasal rubbing, sneezing, eosinophil counts, OVA-specific IgE, and Tfh2 proportions. IL-37 plays a crucial role in modulating Tfh2 cell responses in AR, suggesting a potential therapeutic target for this condition.
变应性鼻炎（AR）由免疫球蛋白E（IgE）介导的针对空气传播变应原的免疫反应引发。近期研究突显了滤泡辅助性T细胞2（Tfh2）在IgE产生中的关键作用。白细胞介素-37（IL-37）已成为固有免疫和炎症过程的内在调节因子。我们旨在研究IL-37在AR发病机制中对Tfh2细胞的调节作用。从AR患者和对照者中采集血样。分别通过酶联免疫吸附测定（ELISA）和流式细胞术检测IL-37水平和Tfh2细胞频率。将分离的Tfh2细胞与初始B细胞进行培养或共培养。使用ELISA、定量实时聚合酶链反应（qRT-PCR）评估IL-37对Tfh2/B细胞的调节作用。建立卵清蛋白（OVA）诱导的AR小鼠模型以探究IL-37在体内的作用。IL-37抑制Tfh2细胞产生IL-4和IL-21，下调CXC趋化因子受体5（CXCR5）和B细胞淋巴瘤6蛋白（Bcl6）mRNA表达，同时上调B淋巴细胞诱导成熟蛋白1（Blimp1）和信号转导子及转录激活子5（STAT5）mRNA。IL-37显著降低B细胞产生的IgE，添加抗IL-18受体α可减轻这种作用。在小鼠模型中，IL-37减少鼻摩擦、打喷嚏、嗜酸性粒细胞计数、OVA特异性IgE和Tfh2比例。IL-37在调节AR中Tfh2细胞反应方面起关键作用，提示其可能是该病的治疗靶点。
