通过输入淋巴管实现 T 细胞的有效归巢需要机械性停滞和整合素支持的趋化因子引导。

Efficient homing of T cells via afferent lymphatics requires mechanical arrest and integrin-supported chemokine guidance.

机构信息

Institute of Immunology, Hannover Medical School, Hannover, Germany.

Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.

出版信息

Nat Commun. 2020 Feb 28;11(1):1114. doi: 10.1038/s41467-020-14921-w.

Abstract

Little is known regarding lymph node (LN)-homing of immune cells via afferent lymphatics. Here, we show, using a photo-convertible Dendra-2 reporter, that recently activated CD4 T cells enter downstream LNs via afferent lymphatics at high frequencies. Intra-lymphatic immune cell transfer and live imaging data further show that activated T cells come to an instantaneous arrest mediated passively by the mechanical 3D-sieve barrier of the LN subcapsular sinus (SCS). Arrested T cells subsequently migrate randomly on the sinus floor independent of both chemokines and integrins. However, chemokine receptors are imperative for guiding cells out of the SCS, and for their subsequent directional translocation towards the T cell zone. By contrast, integrins are dispensable for LN homing, yet still contribute by increasing the dwell time within the SCS and by potentially enhancing T cell sensing of chemokine gradients. Together, these findings provide fundamental insights into mechanisms that control homing of lymph-derived immune cells.

摘要

目前对于通过输入淋巴管归巢到淋巴结(LN)的免疫细胞知之甚少。在这里,我们使用可光转化的 Dendra-2 报告基因显示,最近激活的 CD4 T 细胞以高频率通过输入淋巴管进入下游 LN。淋巴内免疫细胞转移和活体成像数据进一步表明,激活的 T 细胞通过 LN 被膜下窦(SCS)的机械 3D 筛状屏障被动地瞬时停止。随后,被捕获的 T 细胞在窦腔底部随机迁移,与趋化因子和整合素均无关。然而,趋化因子受体对于指导细胞离开 SCS 以及随后朝向 T 细胞区的定向迁移是必不可少的。相比之下,整合素对于 LN 归巢是可有可无的,但仍可以通过增加在 SCS 中的停留时间以及通过潜在地增强 T 细胞对趋化因子梯度的感知来发挥作用。总之,这些发现为控制淋巴来源的免疫细胞归巢的机制提供了基本的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a095/7048855/99cbcfc7091f/41467_2020_14921_Fig1_HTML.jpg

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