自身免疫
免疫学
免疫系统
CTLA-4号机组
背景(考古学)
生物
神经科学
免疫
CD28
医学
T细胞
古生物学
作者
Taku Okazaki,Il‐mi Okazaki
标识
DOI:10.1007/978-981-32-9717-3_8
摘要
Co-receptors cooperatively regulate the function of immune cells to optimize anti-infectious immunity while limiting autoimmunity by providing stimulatory and inhibitory co-signals. Among various co-receptors, those in the CD28/CTLA-4 family play fundamental roles in the regulation of lymphocytes by modulating the strength, quality, and/or duration of the antigen receptor signal. The development of the lethal lymphoproliferative disorder and various tissue-specific autoimmune diseases in mice deficient for CTLA-4 and PD-1, respectively, clearly demonstrates their pivotal roles in the development and the maintenance of immune tolerance. The recent success of immunotherapies targeting CTLA-4 and PD-1 in the treatment of various cancers highlights their critical roles in the regulation of cancer immunity in human. In addition, the development of multifarious autoimmune diseases as immune-related adverse events of anti-CTLA-4 and anti-PD-1/PD-L1 therapies and the successful clinical application of the CD28 blocking therapy using CTLA-4-Ig to the treatment of arthritis assure their crucial roles in the regulation of autoimmunity in human. Accumulating evidences in mice and humans indicate that genetic and environmental factors strikingly modify effects of the targeted inhibition and potentiation of co-signals. In this review, we summarize our current understanding of the roles of CD28, CTLA-4, and PD-1 in autoimmunity. Deeper understandings of the context-dependent and context-independent functions of co-signals are essential for the appropriate usage and the future development of innovative immunomodulatory therapies for a diverse array of diseases.
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