核受体（NR）作为关键的转录因子，在发育、宿主防御和身体稳态等领域协调基本功能。 NR 由于其作为治疗靶点的潜力而受到越来越多的关注，针对 NR 的药物在阻止慢性疾病进展方面显示出显着疗效。因此，这些药物制剂有望用于治疗和控制各种疾病。越来越多的证据强调外泌体衍生的 microRNA (miRNA) 在慢性炎症、疾病进展和治疗耐药中的调节作用，主要是通过调节转录因子，特别是 NR。通过利用蛋白激酶 B (Akt)/哺乳动物雷帕霉素靶点 (mTOR)、核因子 kappa-B (NF-κB)、信号转导子和转录激活子 3 (STAT3) 以及 Wnt/β-连环蛋白信号传导等炎症通路外泌体和 NR 在发育、生理学和病理学方面发挥着关键作用。外泌体的内化调节 NR 并启动多种自分泌或旁分泌信号级联，影响受体细胞的各种过程，如生存、增殖、分化、代谢和细胞防御机制。这篇综合综述仔细研究了外泌体介导的 NR 调节在慢性疾病发病机制中的作用，包括动脉粥样硬化、癌症、糖尿病、肝脏疾病和呼吸系统疾病。此外，它还阐明了外泌体介导的宿主细胞和受体细胞之间通过 NR 进行的通信的分子复杂性，从而导致免疫调节。此外，它概述了外泌体调节的 NR 通路在预防慢性炎症中的影响，描述了当前的局限性，并提供了对未来前景的见解。本综述还提供了关于外泌体及其成分在治疗耐药性出现中的作用的现有证据。© 2024。作者。

Nuclear receptors (NRs) function as crucial transcription factors in orchestrating essential functions within the realms of development, host defense, and homeostasis of body. NRs have garnered increased attention due to their potential as therapeutic targets, with drugs directed at NRs demonstrating significant efficacy in impeding chronic disease progression. Consequently, these pharmacological agents hold promise for the treatment and management of various diseases. Accumulating evidence emphasizes the regulatory role of exosome-derived microRNAs (miRNAs) in chronic inflammation, disease progression, and therapy resistance, primarily by modulating transcription factors, particularly NRs. By exploiting inflammatory pathways such as protein kinase B (Akt)/mammalian target of rapamycin (mTOR), nuclear factor kappa-B (NF-κB), signal transducer and activator of transcription 3 (STAT3), and Wnt/β-catenin signaling, exosomes and NRs play a pivotal role in the panorama of development, physiology, and pathology. The internalization of exosomes modulates NRs and initiates diverse autocrine or paracrine signaling cascades, influencing various processes in recipient cells such as survival, proliferation, differentiation, metabolism, and cellular defense mechanisms. This comprehensive review meticulously examines the involvement of exosome-mediated NR regulation in the pathogenesis of chronic ailments, including atherosclerosis, cancer, diabetes, liver diseases, and respiratory conditions. Additionally, it elucidates the molecular intricacies of exosome-mediated communication between host and recipient cells via NRs, leading to immunomodulation. Furthermore, it outlines the implications of exosome-modulated NR pathways in the prophylaxis of chronic inflammation, delineates current limitations, and provides insights into future perspectives. This review also presents existing evidence on the role of exosomes and their components in the emergence of therapeutic resistance.© 2024. The Author(s).