辅助性 T 细胞 17 免疫在移植中的意义。
Significance of T helper 17 immunity in transplantation.
机构信息
Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
出版信息
Curr Opin Organ Transplant. 2012 Feb;17(1):8-14. doi: 10.1097/MOT.0b013e32834ef4e4.
PURPOSE OF REVIEW
The aim of this review is to provide an overview of significance of T helper 17 (Th17) immunity in acute, chronic and antibody-mediated allograft rejection. The role of Th17 immunity in development of de-novo autoimmunity following transplantation is outlined. It will also consider the impact of Th17 immunity on transplantation tolerance. Potential therapies to target Th17 immunity are discussed.
RECENT FINDINGS
Interleukin17 (IL-17) is produced by a wide variety of immune and non-immune cells in response to injury. IL-17 production by tubular epithelial cells in response to complement activation in acute antibody-mediated rejection may perpetuate immune injury. Th17-dependent de-novo autoimmunity contributes to chronic allograft rejection. Targeting IL-17 not only inhibits Th17 immunity but also attenuates Th1 immunity by affecting the initial recruitment of immune cells to sites of inflammation and modulates innate and adaptive immune responses that ultimately lead to tissue destruction.
SUMMARY
Th17 immunity is now beginning to be appreciated as a set of responses mediated not only by CD4 Th17 cells but a variety of immune cells and a plethora of cytokines that collaborate to mediate immune disorders, including transplant rejection. Development and contribution of de-novo autoimmunity to chronic rejection is increasingly appreciated. The developmental plasticity of Tregs and Th17 cells is a major hurdle to Treg-based cellular therapies for transplantation. Several biologics targeting Th17 immunity are under evaluation for autoimmune disease. It remains to be determined whether these can be used in transplantation to improve outcomes.
目的综述
本文旨在概述辅助性 T 细胞 17（Th17）免疫在急性、慢性和抗体介导的同种异体移植物排斥反应中的意义。概述了 Th17 免疫在移植后新发生自身免疫中的作用。还将考虑 Th17 免疫对移植耐受的影响。讨论了针对 Th17 免疫的潜在治疗方法。
最近的发现
白细胞介素 17（IL-17）是多种免疫和非免疫细胞在受到损伤时产生的。急性抗体介导的排斥反应中补体激活时肾小管上皮细胞产生的 IL-17 可能会持续免疫损伤。Th17 依赖性新发生自身免疫导致慢性同种异体移植排斥反应。靶向 IL-17 不仅抑制 Th17 免疫，而且通过影响免疫细胞向炎症部位的初始募集，调节先天和适应性免疫反应，从而最终导致组织破坏，从而减弱 Th1 免疫。
总结
Th17 免疫现在开始被认为是一组不仅由 CD4 Th17 细胞介导，而且还由多种免疫细胞和大量细胞因子介导的反应，这些反应共同介导免疫紊乱，包括移植排斥反应。新发生自身免疫对慢性排斥反应的发展和贡献越来越受到重视。Treg 和 Th17 细胞的发育可塑性是 Treg 为基础的移植细胞治疗的主要障碍。几种针对 Th17 免疫的生物制剂正在评估用于自身免疫性疾病。尚不确定这些是否可用于移植以改善结果。
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