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靶向 L 型氨基酸转运蛋白 1 治疗难治性哮喘的潜力。

Therapeutic Potential for Intractable Asthma by Targeting L-Type Amino Acid Transporter 1.

机构信息

Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Tochigi 321-0293, Japan.

Department of Disease Model, Research Institute of Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553, Japan.

出版信息

Biomolecules. 2022 Apr 8;12(4):553. doi: 10.3390/biom12040553.

Abstract

Bronchial asthma is a chronic disease characterized by airway inflammation, obstruction, and hyperresponsiveness. CD4 T cells, particularly T helper (Th) 2 cells, and their specific cytokines are important mediators in asthma pathogenesis. However, it has been established that Th subsets, other than Th2, as well as various cell types, including innate lymphoid cells (ILCs), significantly contribute to the development of allergic inflammation. These cells require facilitated amino acid uptake to ensure their full function upon activation. Emerging studies have suggested the potential of pharmacological inhibition of amino acid transporters to inhibit T cell activation and the application of this strategy for treating immunological and inflammatory disorders. In the present review, we explore the possibility of targeting L-type amino acid transporter (LAT) as a novel therapeutic approach for bronchial asthma, including its steroid-resistant endotypes.

摘要

支气管哮喘是一种以气道炎症、阻塞和高反应性为特征的慢性疾病。CD4 T 细胞,特别是辅助性 T 细胞(Th)2 细胞及其特定细胞因子,是哮喘发病机制中的重要介质。然而,已经确定 Th 亚群(除 Th2 以外)以及各种细胞类型,包括先天淋巴细胞(ILCs),对过敏炎症的发展有重要贡献。这些细胞需要促进氨基酸摄取,以确保其在激活时的充分功能。新的研究表明,抑制氨基酸转运体的药理学抑制可能抑制 T 细胞激活,并将这一策略应用于治疗免疫和炎症性疾病。在本综述中,我们探讨了将 L 型氨基酸转运体(LAT)作为一种新型治疗支气管哮喘的方法的可能性,包括其对类固醇耐药的表型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca21/9029068/fbcfa4c8e26c/biomolecules-12-00553-g001.jpg

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