Apolipoprotein A-I mediates function of follicular regulatory T cells and type 2 follicular helper T in allergic rhinitis

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-establis...

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Main Authors: Xiangqian Qiu, MD, Yinhui Zeng, MD, Jinyuan Li, MD, Qingxiang Zeng, PhD, Xi Luo, PhD, Wenlong Liu, PhD
Format: Article
Language:English
Published: Elsevier 2025-04-01
Series:World Allergy Organization Journal
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Online Access:http://www.sciencedirect.com/science/article/pii/S1939455125000201
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author Xiangqian Qiu, MD
Yinhui Zeng, MD
Jinyuan Li, MD
Qingxiang Zeng, PhD
Xi Luo, PhD
Wenlong Liu, PhD
author_facet Xiangqian Qiu, MD
Yinhui Zeng, MD
Jinyuan Li, MD
Qingxiang Zeng, PhD
Xi Luo, PhD
Wenlong Liu, PhD
author_sort Xiangqian Qiu, MD
collection DOAJ
description 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 in vitro 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.
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spelling doaj-art-e31f3fd463804bcc873882bb2a1314922025-08-20T03:40:40ZengElsevierWorld Allergy Organization Journal1939-45512025-04-0118410104510.1016/j.waojou.2025.101045Apolipoprotein A-I mediates function of follicular regulatory T cells and type 2 follicular helper T in allergic rhinitisXiangqian Qiu, MD0Yinhui Zeng, MD1Jinyuan Li, MD2Qingxiang Zeng, PhD3Xi Luo, PhD4Wenlong Liu, PhD5Department of Otolaryngology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, ChinaDepartment of Otolaryngology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, ChinaDepartment of Otolaryngology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, ChinaDepartment of Otolaryngology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, ChinaDepartment of Otolaryngology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, ChinaCorresponding author.; Department of Otolaryngology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, ChinaBackground: 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 in vitro 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.http://www.sciencedirect.com/science/article/pii/S1939455125000201Allergic rhinitisFollicular regulatory T cellsType 2 follicular helper TApolipoprotein AI
spellingShingle Xiangqian Qiu, MD
Yinhui Zeng, MD
Jinyuan Li, MD
Qingxiang Zeng, PhD
Xi Luo, PhD
Wenlong Liu, PhD
Apolipoprotein A-I mediates function of follicular regulatory T cells and type 2 follicular helper T in allergic rhinitis
World Allergy Organization Journal
Allergic rhinitis
Follicular regulatory T cells
Type 2 follicular helper T
Apolipoprotein AI
title Apolipoprotein A-I mediates function of follicular regulatory T cells and type 2 follicular helper T in allergic rhinitis
title_full Apolipoprotein A-I mediates function of follicular regulatory T cells and type 2 follicular helper T in allergic rhinitis
title_fullStr Apolipoprotein A-I mediates function of follicular regulatory T cells and type 2 follicular helper T in allergic rhinitis
title_full_unstemmed Apolipoprotein A-I mediates function of follicular regulatory T cells and type 2 follicular helper T in allergic rhinitis
title_short Apolipoprotein A-I mediates function of follicular regulatory T cells and type 2 follicular helper T in allergic rhinitis
title_sort apolipoprotein a i mediates function of follicular regulatory t cells and type 2 follicular helper t in allergic rhinitis
topic Allergic rhinitis
Follicular regulatory T cells
Type 2 follicular helper T
Apolipoprotein AI
url http://www.sciencedirect.com/science/article/pii/S1939455125000201
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