Vijaykumar D Nimbarte, Shreya S Sonak, Sharda Ishwarkar
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Understanding the Impact of Calcineurin Inhibitors on T Cell Regulation: Mechanisms and Clinical Implications.
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.
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.