MediCity Research Laboratory and Institute of Biomedicine, University of Turku, 20520 Turku, Finland.
Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany.
Sci Immunol. 2019 Mar 29;4(33). doi: 10.1126/sciimmunol.aat0297.
Lymphocytes recirculate continuously between the blood and lymphoid organs, a process that is of fundamental importance for proper functioning of the immune system. The molecular mechanisms underlying lymphocyte trafficking to the spleen remain an enigma. Here, we show that lymphocytes enter the spleen preferentially from vessels in the red pulp rather than the marginal sinus or the vasculature in the white pulp. Ex vivo adhesion assays in mice and humans, together with genetic ablation of Clever-1 in mice, indicate that CD8 T cell and B220 B cell homing to the spleen via the red pulp is Clever-1 dependent. Moreover, absence of Clever-1 leads to down-regulation of the B cell attractant chemokine, CXCL13, on spleen endothelium. CXCL13 is known to guide B cell trafficking to lymphoid organs, and its lack may contribute to the observed decrease in B cell trafficking into the spleen as well. In summary, this study identifies Clever-1 as an important molecule controlling lymphocyte entry into the spleen, along with a critical role for the splenic red pulp in this regulated trafficking. Furthermore, the results demonstrate that location-specific homing-associated molecules guide lymphocyte entry into the spleen.
淋巴细胞在血液和淋巴器官之间持续循环，这一过程对免疫系统的正常功能至关重要。淋巴细胞向脾脏运输的分子机制仍然是一个谜。在这里，我们表明，淋巴细胞优先从红髓中的血管进入脾脏，而不是边缘窦或白髓中的脉管系统。在小鼠和人类中的离体粘附实验，以及在小鼠中对 Clever-1 的基因缺失表明，通过红髓归巢到脾脏的 CD8 T 细胞和 B220 B 细胞依赖于 Clever-1。此外，Clever-1 的缺失导致脾脏内皮细胞上 B 细胞趋化因子 CXCL13 的下调。已知 CXCL13 指导 B 细胞向淋巴器官的运输，其缺失可能导致观察到的 B 细胞向脾脏的运输减少。总之，这项研究确定了 Clever-1 是控制淋巴细胞进入脾脏的重要分子，同时红髓在这种调节性运输中起着关键作用。此外，研究结果表明，位置特异性归巢相关分子指导淋巴细胞进入脾脏。
