The Impact of Mast Cells on the Anatomy, Cellular Communication, and Molecular Immune Network of Lymph Nodes

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.