Park Sehoon, Yi Eunbi, Jeon Jaemyeong, Oh Jinsoo, Xu Zhengmei, Park Se-Ho
College of Life Sciences and Biotechnology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea.
Int J Mol Sci. 2024 Dec 27;26(1):149. doi: 10.3390/ijms26010149.
Bone marrow stromal antigen 2 (BST2) is a host-restriction factor that plays multiple roles in the antiviral defense of innate immune responses, including the inhibition of viral particle release from virus-infected cells. BST2 may also be involved in the endothelial adhesion and migration of monocytes, but its importance in the immune system is still unclear. Immune cell adhesion and migration are closely related to the initiation of immune responses. In this study, we found that the expressions of the lymph node homing marker chemokine receptor 7 (CCR7) and an adhesion molecule intercellular adhesion molecule 1 (ICAM-1) in conventional dendritic cells (cDCs) were associated with BST2 expression. Interestingly, cDCs showed lower chemotactic ability, including velocity and accumulative distance toward chemokine ligand 19 (CCL19) gradient in vitro, compared to wild-type cDCs. cDCs also showed reduced migration and reduced retention capacity in draining lymph nodes in vivo. As a result, cDCs as antigen-presenting cells induced lower antigen-specific B cell and T cell responses compared to cDCs. Notably, mice administered the influenza vaccine via cDCs exhibited substantially inefficient virus clearance compared to mice administered the cDCs vaccine. Therefore, we propose that BST2, which plays a critical role in the effective migration and retention of cDCs, is involved in the development of optimal immunological effects in draining lymph nodes.
骨髓基质抗原2（BST2）是一种宿主限制因子，在先天性免疫反应的抗病毒防御中发挥多种作用，包括抑制病毒颗粒从病毒感染细胞中释放。BST2也可能参与单核细胞的内皮黏附和迁移，但其在免疫系统中的重要性仍不清楚。免疫细胞黏附和迁移与免疫反应的启动密切相关。在本研究中，我们发现常规树突状细胞（cDCs）中淋巴结归巢标志物趋化因子受体7（CCR7）和黏附分子细胞间黏附分子1（ICAM-1）的表达与BST2表达相关。有趣的是，与野生型cDCs相比，cDCs在体外对趋化因子配体19（CCL19）梯度的趋化能力较低，包括速度和累积距离。cDCs在体内引流淋巴结中的迁移和滞留能力也降低。结果，与野生型cDCs相比，作为抗原呈递细胞的cDCs诱导的抗原特异性B细胞和T细胞反应较低。值得注意的是，与接种野生型cDCs疫苗的小鼠相比，通过cDCs接种流感疫苗的小鼠表现出明显低效的病毒清除。因此，我们提出，在cDCs的有效迁移和滞留中起关键作用的BST2参与了引流淋巴结中最佳免疫效应的形成。
