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利用肥大细胞在非传统免疫治疗策略和疫苗佐剂中的作用。

Harnessing the Power of Mast Cells in unconventional Immunotherapy Strategies and Vaccine Adjuvants.

机构信息

Nanotechnology Research Centre, National Research Council Canada, 11421 Saskatchewan Dr, Edmonton, AB T6G 2M9, Canada.

Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB T6G 2E1, Canada.

出版信息

Cells. 2020 Dec 18;9(12):2713. doi: 10.3390/cells9122713.

Abstract

Mast cells are long-lived, granular, myeloid-derived leukocytes that have significant protective and repair functions in tissues. Mast cells sense disruptions in the local microenvironment and are first responders to physical, chemical and biological insults. When activated, mast cells release growth factors, proteases, chemotactic proteins and cytokines thereby mobilizing and amplifying the reactions of the innate and adaptive immune system. Mast cells are therefore significant regulators of homeostatic functions and may be essential in microenvironmental changes during pathogen invasion and disease. During infection by helminths, bacteria and viruses, mast cells release antimicrobial factors to facilitate pathogen expulsion and eradication. Mast cell-derived proteases and growth factors protect tissues from insect/snake bites and exposure to ultraviolet radiation. Finally, mast cells release mediators that promote wound healing in the inflammatory, proliferative and remodelling stages. Since mast cells have such a powerful repertoire of functions, targeting mast cells may be an effective new strategy for immunotherapy of disease and design of novel vaccine adjuvants. In this review, we will examine how certain strategies that specifically target and activate mast cells can be used to treat and resolve infections, augment vaccines and heal wounds. Although these strategies may be protective in certain circumstances, mast cells activation may be deleterious if not carefully controlled and any therapeutic strategy using mast cell activators must be carefully explored.

摘要

肥大细胞是长寿的、颗粒状的、髓系来源的白细胞,在组织中具有重要的保护和修复功能。肥大细胞感知局部微环境的破坏,并对物理、化学和生物损伤做出第一反应。当被激活时,肥大细胞释放生长因子、蛋白酶、趋化蛋白和细胞因子,从而动员和放大先天和适应性免疫系统的反应。因此,肥大细胞是体内平衡功能的重要调节剂,在病原体入侵和疾病过程中的微环境变化中可能是必不可少的。在寄生虫、细菌和病毒感染期间,肥大细胞释放抗菌因子以促进病原体的排出和根除。肥大细胞衍生的蛋白酶和生长因子保护组织免受昆虫/蛇咬伤和紫外线辐射的伤害。最后,肥大细胞释放促进炎症、增殖和重塑阶段伤口愈合的介质。由于肥大细胞具有如此强大的功能组合,靶向肥大细胞可能是疾病免疫治疗和新型疫苗佐剂设计的有效新策略。在这篇综述中,我们将研究特定靶向和激活肥大细胞的某些策略如何用于治疗和解决感染、增强疫苗和治愈伤口。虽然在某些情况下这些策略可能具有保护作用,但如果不仔细控制,肥大细胞的激活可能是有害的,任何使用肥大细胞激活剂的治疗策略都必须仔细探索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fa2/7766453/25e5e758a8a9/cells-09-02713-g001.jpg

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