Department of Immunology and Microbiology, Scripps Research Institute, 10466 North Torrey Pines Rd, La Jolla, CA 92037, United States of America; Yale College, PO Box 208241, New Haven, CT 06520-8241, United States of America.
Department of Immunology and Microbiology, Scripps Research Institute, 10466 North Torrey Pines Rd, La Jolla, CA 92037, United States of America.
Transpl Immunol. 2022 Jun;72:101580. doi: 10.1016/j.trim.2022.101580. Epub 2022 Mar 11.
The purpose of this review is to highlight the potential role for the cluster of differentiation protein 14 (CD14), a co-receptor for toll-like receptor (TLR) signals and as a proximal target for innate immune signals induced during procurement of solid organs for transplantation. CD14 facilitates the detection of multiple pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) by various TLRs. All solid organs used for transplantation are exposed to PAMPs and DAMPs generated during the course of procurement that inevitably trigger injurious inflammatory responses in the donor organ. Multiple experimental animal studies and observations in human organs have provided a solid rationale to consider CD14 blockade as a therapeutic target. CD14 has been recognized for over three decades to play an essential role in innate immune signals associated with sepsis. More recent data now show that genetic deletion or antibody blockade of CD14 can modify ischemic tissue injury in the kidney, liver, heart and lung. Thus, data presented in this review suggest that anti-CD14 directed therapies might be applied to organ preservation strategies in solid organ transplantation.
本篇综述的目的在于强调分化簇蛋白 14（CD14）的潜在作用，CD14 是 Toll 样受体（TLR）信号的共受体，也是在获取用于移植的实体器官过程中诱导的固有免疫信号的近端靶标。CD14 有助于多种 TLR 检测多种病原体相关分子模式（PAMP）和损伤相关分子模式（DAMP）。用于移植的所有实体器官在获取过程中都会暴露于 PAMP 和 DAMPs，这些 DAMPs 不可避免地会引发供体器官的损伤性炎症反应。多项实验动物研究和人类器官观察为考虑 CD14 阻断作为治疗靶点提供了坚实的依据。三十多年来，CD14 一直被认为在与败血症相关的固有免疫信号中发挥重要作用。最近的数据表明，CD14 的基因缺失或抗体阻断可以改变肾脏、肝脏、心脏和肺部的缺血组织损伤。因此，本综述中提出的研究数据表明，抗 CD14 定向治疗可能适用于实体器官移植中的器官保存策略。
