Understanding the Impact of Calcineurin Inhibitors on T Cell Regulation: Mechanisms and Clinical Implications.

IF 0.9 4区 医学 Q4 IMMUNOLOGY
Vijaykumar D Nimbarte, Shreya S Sonak, Sharda Ishwarkar
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引用次数: 0

Abstract

Calcineurin inhibitors (CNIs) are key in immunosuppressive therapy for organ transplantation and autoimmune diseases by modulating T cell activation. This review details how CNIs inhibit T cell receptor signaling, cytokine production, and T cell differentiation by binding to intracellular proteins, thus preventing the activation of NFAT, a critical transcription factor. The clinical benefits of CNIs include preventing graft rejection and controlling autoimmune responses, but they also have significant side effects such as nephrotoxicity, neurotoxicity, hypertension, hyperlipidemia, and increased risk of infections and malignancies. Optimizing CNI use involves developing safer versions, personalizing regimens, and combining therapies to lower doses and reduce side effects. Understanding CNIs' interactions with T cells can improve therapy outcomes and guide the creation of targeted treatments. Effective patient monitoring and management are essential to mitigate toxicities. Future research should focus on CNIs' pharmacodynamics and pharmacokinetics in developing next-generation immunosuppressants, and personalized and combination therapies to enhance safety and efficacy, ultimately improving patient outcomes and quality of life.

了解钙调磷酸酶抑制剂对T细胞调节的影响:机制和临床意义。
钙调磷酸酶抑制剂(CNIs)通过调节T细胞活化在器官移植和自身免疫性疾病的免疫抑制治疗中发挥关键作用。本文详细介绍了CNIs如何通过与细胞内蛋白结合来抑制T细胞受体信号传导、细胞因子产生和T细胞分化,从而阻止关键转录因子NFAT的激活。CNIs的临床益处包括预防移植物排斥反应和控制自身免疫反应,但它们也有显著的副作用,如肾毒性、神经毒性、高血压、高脂血症和增加感染和恶性肿瘤的风险。优化CNI的使用包括开发更安全的版本,个性化的方案,并结合治疗以降低剂量和减少副作用。了解CNIs与T细胞的相互作用可以改善治疗效果,并指导靶向治疗的创建。有效的患者监测和管理对于减轻毒性至关重要。未来的研究应关注cni的药效学和药代动力学,以开发下一代免疫抑制剂,以及个性化和联合治疗,以提高安全性和有效性,最终改善患者的预后和生活质量。
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来源期刊
CiteScore
2.60
自引率
0.00%
发文量
14
审稿时长
>12 weeks
期刊介绍: Immunology covers a broad spectrum of investigations at the genes, molecular, cellular, organ and system levels to reveal defense mechanisms against pathogens as well as protection against tumors and autoimmune diseases. The great advances in immunology in recent years make this field one of the most dynamic and rapidly growing in medical sciences. Critical ReviewsTM in Immunology (CRI) seeks to present a balanced overview of contemporary adaptive and innate immune responses related to autoimmunity, tumor, microbe, transplantation, neuroimmunology, immune regulation and immunotherapy from basic to translational aspects in health and disease. The articles that appear in CRI are mostly obtained by invitations to active investigators. But the journal will also consider proposals from the scientific community. Interested investigators should send their inquiries to the editor before submitting a manuscript.
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