研究动态
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实体器官移植中的调节性 B 细胞:从免疫监测到免疫治疗。

Regulatory B Cells in Solid Organ Transplantation: From Immune Monitoring to Immunotherapy.

发表日期:2023 Oct 02
作者: Charbel Elias, Chuxiao Chen, Aravind Cherukuri
来源: TRANSPLANTATION

摘要:

调节性 B 细胞 (Breg) 在包括移植在内的多种疾病环境中调节免疫反应。尽管缺乏特定的表型标记或转录因子,但它们在移植中的重要性通过它们延长实验同种异体移植物存活的能力、它们作为免疫监测工具的临床用途的可能性以及它们形成细胞基础的令人兴奋的前景而得到强调。治疗。白细胞介素 (IL)-10 表达仍然是 Breg 使用最广泛的标记。已经在小鼠和人类中描述了表达这种“标志性 Breg 细胞因子”的几个具有不同表型的 Breg 亚群。尽管 T 细胞免疫球蛋白和粘蛋白家族 1 是最具包容性和功能性的标记物,可解释具有不同作用机制的小鼠 Breg,但 T 细胞免疫球蛋白和粘蛋白家族 1 作为人类 Breg 标记物的重要性仍需进一步研究。被探索。尽管本综述的主要焦点是 Breg 在临床移植中的作用,但 B 细胞对免疫反应和临床结果的净调节作用是 Breg 和效应 B 细胞平衡功能的结果。支持这一观点的是,B 细胞 IL-10/肿瘤坏死因子 α 比率可预测肾移植和肝移植中的免疫反应性和临床结果。使用 IL-10/肿瘤坏死因子 α 比率评估 Breg:B 效应器平衡可以识别需要更多免疫抑制的患者,并为潜在疗法提供机制见解。总之,目前我们对小鼠和人类 Breg 的理解取得的进展将为未来的明确临床研究铺平道路,旨在测试它们的免疫监测和作为治疗靶点。版权所有 © 2023 Wolters Kluwer Health, Inc. 保留所有权利。
Regulatory B cells (Breg) modulate the immune response in diverse disease settings including transplantation. Despite the lack of a specific phenotypic marker or transcription factor, their significance in transplantation is underscored by their ability to prolong experimental allograft survival, the possibility for their clinical use as immune monitoring tools, and the exciting prospect for them to form the basis for cell therapy. Interleukin (IL)-10 expression remains the most widely used marker for Breg. Several Breg subsets with distinct phenotypes that express this "signature Breg cytokine" have been described in mice and humans. Although T-cell immunoglobulin and mucin family-1 is the most inclusive and functional marker that accounts for murine Breg with disparate mechanisms of action, the significance of T-cell immunoglobulin and mucin family-1 as a marker for Breg in humans still needs to be explored. Although the primary focus of this review is the role of Breg in clinical transplantation, the net modulatory effect of B cells on the immune response and clinical outcomes is the result of the balancing functions of both Breg and effector B cells. Supporting this notion, B-cell IL-10/tumor necrosis factor α ratio is shown to predict immunologic reactivity and clinical outcomes in kidney and liver transplantation. Assessment of Breg:B effector balance using their IL-10/tumor necrosis factor α ratio may identify patients that require more immunosuppression and provide mechanistic insights into potential therapies. In summary, current advances in our understanding of murine and human Breg will pave way for future definitive clinical studies aiming to test them for immune monitoring and as therapeutic targets.Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.