5-Hydroxytryptamine Limits Pulmonary Arterial Hypertension Progression by Regulating Th17/Treg Balance.

IF 1.7 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Junli Han, Lianghe Wang, Li Wang, Hua Lei
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Abstract

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.

5-羟色胺通过调节Th17/Treg平衡限制肺动脉高压进展。
肺动脉高压(PAH)是一种进行性疾病,缺乏有效的治疗方法。因此,对多环芳烃发病机制的进一步研究将有助于探索新的治疗方法。辅助性T 17 (Th17)细胞介导的促炎反应的增加和调节性T (Treg)细胞介导的抗炎作用的降低加剧了PAH的进展。越来越多的证据表明,5-羟色胺(5-HT)与Th17和Treg极化密切相关。这里,在缺氧诱导的CD4 + T细胞中发现5-HT的减少。缺氧也导致Treg细胞减少,Th17细胞增加,但5-HT的增加恢复了Th17/Treg平衡,证实缺氧通过诱导5-HT降低破坏了Th17/Treg平衡。此外,我们发现5- ht恢复的Th17/Treg平衡减轻了原发性肺动脉平滑肌细胞(PASMC)的增殖、迁移和收缩,这是PAH血管重构的重要因素。综上所述,我们的研究结果表明,缺氧诱导的5-HT下降干扰了Th17/Treg的平衡,从而影响了pasmc的生物功能,从而加速了PAH的发展。5- ht介导的Th17/Treg平衡有望作为PAH治疗的一种新的免疫疗法。
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来源期刊
CiteScore
3.50
自引率
5.00%
发文量
247
审稿时长
2 months
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. The main aim of the Society’s journals is to advance the pharmaceutical sciences with research reports, information exchange, and high-quality discussion. The average review time for articles submitted to the journals is around one month for first decision. The complete texts of all of the Society’s journals can be freely accessed through J-STAGE. The Society’s editorial committee hopes that the content of its journals will be useful to your research, and also invites you to submit your own work to the journals.
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