{"title":"5-羟色胺通过调节Th17/Treg平衡限制肺动脉高压进展。","authors":"Junli Han, Lianghe Wang, Li Wang, Hua Lei","doi":"10.1248/bpb.b24-00831","DOIUrl":null,"url":null,"abstract":"<p><p>Pulmonary arterial hypertension (PAH) is a progressive disorder that lacks a validated and effective therapy. Thus, further investigation of the pathogenesis of PAH will help explore novel treatments. The increase in T helper 17 (Th17) cell-mediated pro-inflammatory response and reduction of regulatory T (Treg) cell-mediated anti-inflammatory effect exacerbates PAH progression. Increasing evidence indicates that 5-hydroxytryptamine (5-HT) is closely related to Th17 and Treg polarization. Here, a decrease of 5-HT was found in hypoxia-induced CD4 + T cells. Hypoxia also resulted in a reduction in Treg cells and an increase in Th17 cells, but the addition of 5-HT rescued Th17/Treg balance, confirming that hypoxia destroyed Th17/Treg balance by inducing a 5-HT decrease. Furthermore, we found that 5-HT-restored Th17/Treg balance mitigated primary pulmonary artery smooth muscle cell (PASMC) proliferation, migration, and contraction, which are important factors in vascular remodeling in PAH. In summary, our findings demonstrate that hypoxia-induced 5-HT decline interferes with the balance of Th17/Treg, which affects the biofunction of PASMCs, thus accelerating PAH development. 5-HT-mediated Th17/Treg balance is expected to act as a novel immunotherapy for PAH treatment.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 5","pages":"555-562"},"PeriodicalIF":1.7000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"5-Hydroxytryptamine Limits Pulmonary Arterial Hypertension Progression by Regulating Th17/Treg Balance.\",\"authors\":\"Junli Han, Lianghe Wang, Li Wang, Hua Lei\",\"doi\":\"10.1248/bpb.b24-00831\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Pulmonary arterial hypertension (PAH) is a progressive disorder that lacks a validated and effective therapy. Thus, further investigation of the pathogenesis of PAH will help explore novel treatments. The increase in T helper 17 (Th17) cell-mediated pro-inflammatory response and reduction of regulatory T (Treg) cell-mediated anti-inflammatory effect exacerbates PAH progression. Increasing evidence indicates that 5-hydroxytryptamine (5-HT) is closely related to Th17 and Treg polarization. Here, a decrease of 5-HT was found in hypoxia-induced CD4 + T cells. Hypoxia also resulted in a reduction in Treg cells and an increase in Th17 cells, but the addition of 5-HT rescued Th17/Treg balance, confirming that hypoxia destroyed Th17/Treg balance by inducing a 5-HT decrease. Furthermore, we found that 5-HT-restored Th17/Treg balance mitigated primary pulmonary artery smooth muscle cell (PASMC) proliferation, migration, and contraction, which are important factors in vascular remodeling in PAH. In summary, our findings demonstrate that hypoxia-induced 5-HT decline interferes with the balance of Th17/Treg, which affects the biofunction of PASMCs, thus accelerating PAH development. 5-HT-mediated Th17/Treg balance is expected to act as a novel immunotherapy for PAH treatment.</p>\",\"PeriodicalId\":8955,\"journal\":{\"name\":\"Biological & pharmaceutical bulletin\",\"volume\":\"48 5\",\"pages\":\"555-562\"},\"PeriodicalIF\":1.7000,\"publicationDate\":\"2025-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biological & pharmaceutical bulletin\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1248/bpb.b24-00831\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biological & pharmaceutical bulletin","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1248/bpb.b24-00831","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
5-Hydroxytryptamine Limits Pulmonary Arterial Hypertension Progression by Regulating Th17/Treg Balance.
Pulmonary arterial hypertension (PAH) is a progressive disorder that lacks a validated and effective therapy. Thus, further investigation of the pathogenesis of PAH will help explore novel treatments. The increase in T helper 17 (Th17) cell-mediated pro-inflammatory response and reduction of regulatory T (Treg) cell-mediated anti-inflammatory effect exacerbates PAH progression. Increasing evidence indicates that 5-hydroxytryptamine (5-HT) is closely related to Th17 and Treg polarization. Here, a decrease of 5-HT was found in hypoxia-induced CD4 + T cells. Hypoxia also resulted in a reduction in Treg cells and an increase in Th17 cells, but the addition of 5-HT rescued Th17/Treg balance, confirming that hypoxia destroyed Th17/Treg balance by inducing a 5-HT decrease. Furthermore, we found that 5-HT-restored Th17/Treg balance mitigated primary pulmonary artery smooth muscle cell (PASMC) proliferation, migration, and contraction, which are important factors in vascular remodeling in PAH. In summary, our findings demonstrate that hypoxia-induced 5-HT decline interferes with the balance of Th17/Treg, which affects the biofunction of PASMCs, thus accelerating PAH development. 5-HT-mediated Th17/Treg balance is expected to act as a novel immunotherapy for PAH treatment.
期刊介绍:
Biological and Pharmaceutical Bulletin (Biol. Pharm. Bull.) began publication in 1978 as the Journal of Pharmacobio-Dynamics. It covers various biological topics in the pharmaceutical and health sciences. A fourth Society journal, the Journal of Health Science, was merged with Biol. Pharm. Bull. in 2012.
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