小柯机器人

研究揭示分散免疫稳态的成因
2021-03-19 15:59

美国明尼苏达大学David Masopust研究团队取得一项新突破。他们发现了驻留T细胞是产生分散免疫稳态的原因。相关论文于2021年3月17日在线发表在《自然》杂志上。

研究人员探究了如何恢复成年小鼠组织的免疫力,并解决耐用性、可扩展性和对器官细胞形成的影响。在抗病毒T细胞免疫中,研究人员发现在感染后长达450天后驻留记忆T细胞仍可持久存在。驻留T细胞一经形成就不再需要T细胞受体来维持或保持平衡的效应因子样状态。尽管驻留记忆T细胞无限期地占据大多数粘膜器官,但通过手术分离共生联体小鼠揭示了血源性效应记忆T细胞的组织常驻起源,而循环记忆T细胞在某些器官中缓慢地对组织免疫做出了实质性贡献。

在进行系列免疫或与pet-shop小鼠共栖之后,研究人员发现在大多数组织中,组织柔韧性(组织改变免疫细胞比例的能力)能够增加组织驻留记忆T细胞,而不会对已有的抗病毒T细胞免疫产生损害。通过这些发现,研究人员证明了组织驻留T细胞和器官柔韧性是固有免疫和适应性免疫稳态的基础。

免疫系统的增强与微生物相称达到内脏器官细胞密度的25%。许多白细胞种群都在非淋巴器官内采用了组织驻留程序。因此,驻留而非更新或再循环的T细胞是非淋巴免疫监测的典型代表,而器官则是可以容纳整个生命中细胞免疫系统不断扩展的灵活储存库。尽管造血功能恢复了免疫系统的某些功能,但非淋巴器官仍维持了持久的组织自主性细胞免疫功能,这有助于形成逐步分散的机体免疫稳态。

据介绍,在后生动物中,由专门的器官调控特定的功能,这些器官形成于发育早期,占据了不连续的位置并且通常大小保持不变。成年免疫系统来源于具有维持自我更新潜力的造血小生境,并在成熟后逐渐分布于全身,以监测环境扰动、调节组织稳态并介入机体防御。

附:英文原文

Title: Expansible residence decentralizes immune homeostasis

Author: Sathi Wijeyesinghe, Lalit K. Beura, Mark J. Pierson, J. Michael Stolley, Omar A. Adam, Roland Ruscher, Elizabeth M. Steinert, Pamela C. Rosato, Vaiva Vezys, David Masopust

Issue&Volume: 2021-03-17

Abstract: In metazoans, specific tasks are relegated to dedicated organs that are established early in development, occupy discrete locations and typically remain fixed in size. The adult immune system arises from a centralized haematopoietic niche that maintains self-renewing potential1,2, and—upon maturation—becomes distributed throughout the body to monitor environmental perturbations, regulate tissue homeostasis and mediate organism-wide defence. Here we examine how immunity is integrated within adult mouse tissues, and address issues of durability, expansibility and contributions to organ cellularity. Focusing on antiviral T cell immunity, we observed durable maintenance of resident memory T cells up to 450 days after infection. Once established, resident T cells did not require the T cell receptor for survival or retention of a poised, effector-like state. Although resident memory indefinitely dominated most mucosal organs, surgical separation of parabiotic mice revealed a tissue-resident provenance for blood-borne effector memory T cells, and circulating memory slowly made substantial contributions to tissue immunity in some organs. After serial immunizations or cohousing with pet-shop mice, we found that in most tissues, tissue pliancy (the capacity of tissues to vary their proportion of immune cells) enables the accretion of tissue-resident memory, without axiomatic erosion of pre-existing antiviral T cell immunity. Extending these findings, we demonstrate that tissue residence and organ pliancy are generalizable aspects that underlie homeostasis of innate and adaptive immunity. The immune system grows commensurate with microbial experience, reaching up to 25% of visceral organ cellularity. Regardless of the location, many populations of white blood cells adopted a tissue-residency program within nonlymphoid organs. Thus, residence—rather than renewal or recirculation—typifies nonlymphoid immune surveillance, and organs serve as pliant storage reservoirs that can accommodate continuous expansion of the cellular immune system throughout life. Although haematopoiesis restores some elements of the immune system, nonlymphoid organs sustain an accrual of durable tissue-autonomous cellular immunity that results in progressive decentralization of organismal immune homeostasis.

DOI: 10.1038/s41586-021-03351-3

Source: https://www.nature.com/articles/s41586-021-03351-3

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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