英国剑桥大学Menna R. Clatworthy等研究人员合作发现，巨噬细胞和痛觉感受器神经元在有孔毛细血管周围形成哨兵单元，来保护滑膜免受循环免疫挑战。相关论文于2024年11月25日在线发表在《自然—免疫学》杂志上。

研究人员通过全程滑膜成像揭示了位于滑膜外围衬里–下衬界面的PV1⁺有孔毛细血管。循环中的免疫复合物（IC）从这些PV1⁺毛细血管中渗出，痛觉感受器神经元和三种不同的巨噬细胞亚群在它们周围形成了哨兵单元。巨噬细胞对系统性IC挑战表现出亚群特异性的反应；LYVE1⁺CX3CR1⁺巨噬细胞通过白介素-1β调控中性粒细胞招募，并激活降钙素基因相关肽⁺（CGRP⁺）痛觉感受器神经元。

相比之下，主要组织相容性复合物II类⁺CD11c⁺（MHCII⁺CD11c⁺）和MHCII⁺CD11c^–间质巨噬细胞在系统性免疫刺激的作用下围绕PV1⁺毛细血管形成紧密的簇，这一特征被痛觉感受器分泌的CGRP增强。总的来说，研究人员确定了滑膜PV1⁺毛细血管的解剖位置，并揭示了亚群特异性的巨噬细胞–痛觉感受器跨细胞信号通路，形成了保护滑膜免受循环免疫挑战的血–关节屏障。

据悉，多种系统性病理，包括感染性和自身免疫性疾病，常伴随关节疼痛或炎症，这通常是由循环介导的。然而，这些刺激如何进入关节并触发炎症仍不清楚。

附：英文原文

Title: Macrophages and nociceptor neurons form a sentinel unit around fenestrated capillaries to defend the synovium from circulating immune challenge

Author: Hasegawa, Tetsuo, Lee, Colin Y. C., Hotchen, Andrew J., Fleming, Aaron, Singh, Rahul, Suzuki, Kunimichi, Yuzaki, Michisuke, Watanabe, Masahiko, Birch, Mark A., McCaskie, Andrew W., Lnrt, Nikolett, Tth, Krisztina, Dnes, dm, Liu, Zhaoyuan, Ginhoux, Florent, Richoz, Nathan, Clatworthy, Menna R.

Issue&Volume: 2024-11-25

Abstract: A wide variety of systemic pathologies, including infectious and autoimmune diseases, are accompanied by joint pain or inflammation, often mediated by circulating immune complexes (ICs). How such stimuli access joints and trigger inflammation is unclear. Whole-mount synovial imaging revealed PV1+ fenestrated capillaries at the periphery of the synovium in the lining–sublining interface. Circulating ICs extravasated from these PV1+ capillaries, and nociceptor neurons and three distinct macrophage subsets formed a sentinel unit around them. Macrophages showed subset-specific responses to systemic IC challenge; LYVE1+CX3CR1+ macrophages orchestrated neutrophil recruitment and activated calcitonin gene-related peptide+ (CGRP+) nociceptor neurons via interleukin-1β. In contrast, major histocompatibility complex class II+CD11c+ (MHCII+CD11c+) and MHCII+CD11c– interstitial macrophages formed tight clusters around PV1+ capillaries in response to systemic immune stimuli, a feature enhanced by nociceptor-derived CGRP. Altogether, we identify the anatomical location of synovial PV1+ capillaries and subset-specific macrophage–nociceptor cross-talk that forms a blood–joint barrier protecting the synovium from circulating immune challenges.

DOI: 10.1038/s41590-024-02011-8

Source: https://www.nature.com/articles/s41590-024-02011-8