载脂蛋白A-I介导变应性鼻炎中滤泡调节性T细胞和2型滤泡辅助性T细胞的功能。
Apolipoprotein A-I mediates function of follicular regulatory T cells and type 2 follicular helper T in allergic rhinitis.
作者信息
Qiu Xiangqian, Zeng Yinhui, Li Jinyuan, Zeng Qingxiang, Luo Xi, Liu Wenlong
机构信息
Department of Otolaryngology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, China.
出版信息
World Allergy Organ J. 2025 Mar 24;18(4):101045. doi: 10.1016/j.waojou.2025.101045. eCollection 2025 Apr.
BACKGROUND
The follicular regulatory T cells (Tfr) and type 2 follicular helper T (Tfh2) play important roles in the pathogenesis of allergic rhinitis (AR). However, its detailed mechanism underlying the regulation of between Tfr and Tfh in AR is unclear. Apolipoprotein AI (Apo-AI), a well-established anti-inflammatory protein, exhibits anti-inflammatory effects on neutrophils, monocytes, macrophages, eosinophils, and type 2 innate lymphoid cells. We sought to investigate the interaction and mechanism between Apo-AI and Tfr/Tfh2 in AR.
METHODS
The peripheral Tfh2 and Tfr cells were detected and compared by flow cytometry and their correlation with serum Apo-AI protein expression were analyzed. The effect of Apo-AI on Tfh2 and Tfr cells were determined through detection of functional cytokines and key transcription factors by enzyme-linked immunosorbent assay (ELSIA) or polymerase chain reaction (PCR). A Tfr-Tfh2-B cell coculture system was adopted to investigate the role of Apo-AI. Apo-AI knockout AR mice model was established to verify the results of studies.
RESULTS
The serum Apo-AI concentration was positively correlated with the blood frequencies of Tfr cells and negatively correlated with the blood frequencies of Tfh2 cells in AR patients. Apo-AI inhibited IL-4 and IL-21 protein expression by Tfh2 and promoted IL-10 and TGF-beta protein expression by Tfr. In Tfr-Tfh2-B cell coculture system, Apo-AI attenuated the expression of IL-4, IL-21 and activation-induced cytidine deaminase through inducible costimulator (ICOS)/inducible costimulator ligand (ICOSL) pathways. Apo-AI partially restored the suppressive function of AR-derived Tfr cells. Apo-AI knockout AR mice presented with elevated blood Tfh2 frequencies and decreased blood Tfr frequencies, while administration of anti-ICOSL reversed the effect of Apo-AI.
CONCLUSION
Apo-AI alleviates AR through the regulation of the function of Tfh2 and Tfr, which may serve as a potential treatment target for AR.
背景
滤泡调节性T细胞（Tfr）和2型滤泡辅助性T细胞（Tfh2）在变应性鼻炎（AR）的发病机制中起重要作用。然而，AR中Tfr和Tfh之间调节的详细机制尚不清楚。载脂蛋白AI（Apo-AI）是一种公认的抗炎蛋白，对中性粒细胞、单核细胞、巨噬细胞、嗜酸性粒细胞和2型固有淋巴细胞具有抗炎作用。我们试图研究Apo-AI与AR中Tfr/Tfh2之间的相互作用及其机制。
方法
通过流式细胞术检测并比较外周血Tfh2和Tfr细胞，并分析它们与血清Apo-AI蛋白表达的相关性。通过酶联免疫吸附测定（ELSIA）或聚合酶链反应（PCR）检测功能性细胞因子和关键转录因子，确定Apo-AI对Tfh2和Tfr细胞的影响。采用Tfr-Tfh2-B细胞共培养系统研究Apo-AI的作用。建立Apo-AI基因敲除的AR小鼠模型以验证研究结果。
结果
AR患者血清Apo-AI浓度与Tfr细胞的血液频率呈正相关，与Tfh2细胞的血液频率呈负相关。Apo-AI抑制Tfh2产生的IL-4和IL-21蛋白表达，并促进Tfr产生的IL-10和TGF-β蛋白表达。在Tfr-Tfh2-B细胞共培养系统中，Apo-AI通过诱导性共刺激分子（ICOS）/诱导性共刺激分子配体（ICOSL）途径减弱IL-4、IL-21和活化诱导的胞苷脱氨酶的表达。Apo-AI部分恢复了AR来源的Tfr细胞的抑制功能。Apo-AI基因敲除的AR小鼠外周血Tfh2频率升高，Tfr频率降低，而给予抗ICOSL可逆转Apo-AI的作用。
结论
Apo-AI通过调节Tfh2和Tfr的功能减轻AR，这可能成为AR的潜在治疗靶点。
Zotero 插件