Elieh-Ali-Komi Daniel, Maurer Marcus, Siebenhaar Frank
Institute of Allergology, Charité - Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany.
Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Immunology and Allergology, Berlin, Germany.
Clin Rev Allergy Immunol. 2025 Apr 2;68(1):35. doi: 10.1007/s12016-025-09050-5.
Lymph nodes (LNs) are ovoid-shape capsulated structures interposed along the lymphatic vessels. Owing to their unique architecture, LNs place immune cell types in distinct compartments allowing effective contact of antigens to them. Their efficient function results in the concentration of antigens and bridging of antigen-presenting cells like DCs and B cells and cells of adaptive immunity (circulating B and T lymphocytes remaining in LNs to monitor antigens) to coordinate efficient immune responses. In a healthy LN, B cells are primarily clustered in lymphoid follicles, whereas T cells are organized in the deeper paracortex region. Mast cells (MCs) are among the immune cells; their normal presence or pathologic infiltration has been reported in LNs. MCs enter LNs through afferent lymphatic vessels and can be found in all compartments, ranging from subcapsular sinus to the deepest sections of medullary sinus; however, they are commonly found in the T cell zone and medullary sinus but rarely in follicles. In pathologies with LN involvement and solid tumors, features like MC accumulation and the anatomical region of accumulation within LNs differ based on the type of tumor and the organ. Moreover, MC accumulation in LNs may influence the trafficking of other cell types and immune responses. MCs out of LNs can facilitate the migration of DCs into LN, which is crucial for orchestrating immune responses, especially in vaccination; moreover, MCs play a role in the induction of peripheral tolerance. MC-released mediators including TNF from tissue-resident MCs and tryptase from LN-MCs mediate hyperplasia and extension of LN vasculature, respectively. MCs support lymphangiogenesis by releasing VEGF-C and VEGF-D in vivo. Further research on the role of MCs in LNs is anticipated due to the development of pharmaceuticals that impact MC survival or inhibit their activation. In this review, we summarize the current literature regarding the outcomes of MC presence in LNs with a focus on the MC-mediated immune responses in two categories: direct cell-to-cell and mediator-based interactions.
淋巴结（LNs）是沿淋巴管分布的椭圆形被膜结构。由于其独特的结构，淋巴结将免疫细胞类型置于不同的隔室中，使抗原能与它们有效接触。其高效功能导致抗原的聚集以及抗原呈递细胞（如树突状细胞和B细胞）与适应性免疫细胞（留在淋巴结中监测抗原的循环B和T淋巴细胞）之间的连接，以协调有效的免疫反应。在健康的淋巴结中，B细胞主要聚集在淋巴滤泡中，而T细胞则组织在更深的副皮质区域。肥大细胞（MCs）是免疫细胞之一；已有报道称它们在淋巴结中正常存在或发生病理浸润。肥大细胞通过输入淋巴管进入淋巴结，可在从被膜下窦到髓窦最深处的所有隔室中发现；然而，它们通常存在于T细胞区和髓窦，而在滤泡中很少见。在涉及淋巴结的病理情况和实体瘤中，肥大细胞积累的特征以及在淋巴结内积累的解剖区域因肿瘤类型和器官而异。此外，淋巴结中的肥大细胞积累可能会影响其他细胞类型的运输和免疫反应。淋巴结外的肥大细胞可促进树突状细胞迁移到淋巴结，这对于协调免疫反应至关重要，尤其是在疫苗接种中；此外，肥大细胞在诱导外周耐受中发挥作用。肥大细胞释放的介质，包括组织驻留肥大细胞释放的肿瘤坏死因子（TNF）和淋巴结肥大细胞释放的类胰蛋白酶，分别介导淋巴结血管的增生和扩张。肥大细胞在体内通过释放血管内皮生长因子C（VEGF-C）和血管内皮生长因子D（VEGF-D）支持淋巴管生成。由于影响肥大细胞存活或抑制其激活的药物的开发，预计将对肥大细胞在淋巴结中的作用进行进一步研究。在本综述中，我们总结了关于肥大细胞在淋巴结中存在的结果的当前文献，重点关注肥大细胞介导的免疫反应的两类：直接细胞间相互作用和基于介质的相互作用。
