Network Of Lymph Nodes Research Articles

Lymph node medulla regulates the spatiotemporal unfolding of resident dendritic cell networks

Unlike macrophage networks composed of long-lived tissue-resident cells within specific niches, conventional dendritic cells (cDCs) that generate a 3D network in lymph nodes (LNs) are short lived and continuously replaced by DC precursors (preDCs) from the bone marrow (BM). Here, we examined whether specific anatomical niches exist within which preDCs differentiate toward immature cDCs. In situ photoconversion and Prtn3-based fate-tracking revealed that the LN medullary cords are preferential entry sites for preDCs, serving as specific differentiation niches. Repopulation and fate-tracking approaches demonstrated that the cDC1 network unfolded from the medulla along the vascular tree toward the paracortex. During inflammation, collective maturation and migration of resident cDC1s to the paracortex created discontinuity in the medullary cDC1 network and temporarily impaired responsiveness. The decrease in local cDC1 density resulted in higher Flt3L availability in the medullary niche, which accelerated cDC1 development to restore the network. Thus, the spatiotemporal development of the cDC1 network is locally regulated in dedicated LN niches via sensing of cDC1 densities.

Topological Structure and Robustness of the Lymph Node Conduit System

Fibroblastic reticular cells (FRCs) form a road-like cellular network in lymph nodes (LNs) that provides essential chemotactic, survival, and regulatory signals for immune cells. While the topological characteristics of the FRC network have been elaborated, the network properties of the micro-tubular conduit system generated by FRCs, which drains lymph fluid through a pipeline-like system to distribute small molecules and antigens, has remained unexplored. Here, we quantify the crucial 3D morphometric parameters and determine the topological properties governing the structural organization of the intertwined networks. We find that the conduit system exhibits lesser small-worldness and lower resilience to perturbation compared to the FRC network, while the robust topological organization of both networks is maintained in a lymphotoxin-β-receptor-independent manner. Overall, the high-resolution topological analysis of the "roads-and-pipes" networks highlights essential parameters underlying the functional organization of LN micro-environments and will, hence, advance the development of multi-scale LN models.

Graph Theory-Based Analysis of the Lymph Node Fibroblastic Reticular Cell Network.

Secondary lymphoid organs have developed segregated niches that are able to initiate and maintain effective immune responses. Such global organization requires tight control of diverse cellular components, specifically those that regulate lymphocyte trafficking. Fibroblastic reticular cells (FRCs) form a densely interconnected network in lymph nodes and provide key factors necessary for T cell migration and retention, and foster subsequent interactions between T cells and dendritic cells. Development of integrative systems biology approaches has made it possible to elucidate this multilevel complexity of the immune system. Here, we present a graph theory-based analysis of the FRC network in murine lymph nodes, where generation of the network topology is performed using high-resolution confocal microscopy and 3D reconstruction. This approach facilitates the analysis of physical cell-to-cell connectivity, and estimation of topological robustness and global behavior of the network when it is subjected to perturbation in silico.

The Surgical Anatomy of the Inguinal Lymphatics

Knowledge of the lymphatic system plays critical importance in surgical oncology. The study of the lymphatic system and its role in tumor metastasis continues to advance with new anatomical and surgical studies, and with a new study, we can gain a better understanding on how aggressive surgeons need to be with nodal dissection while balancing the complications with overly aggressive approaches. The lymphatics of the inguinal region represent a network of lymph nodes and vessels, which act as the bridge among the lower extremities, pelvis, perineum, and rest of the body. These lymph nodes are of particular importance in the metastatic spread of genitourinary and lower gastrointestinal epithelial cancer to the inguinal nodes. The aim of this article is to reveal the literature with regard to the inguinal lymph nodes and their relation in various carcinomas.

Plasmacytoid DCs help lymph node DCs to induce anti-HSV CTLs

Antiviral cell–mediated immunity is initiated by the dendritic cell (DC) network in lymph nodes (LNs). Plasmacytoid DCs (pDCs) are known to migrate to inflamed LNs and produce interferon (IFN)-α, but their other roles in antiviral T cell immunity are unclear. We report that LN-recruited pDCs are activated to create local immune fields that generate antiviral cytotoxic T lymphocytes (CTLs) in association with LNDCs, in a model of cutaneous herpes simplex virus (HSV) infection. Although pDCs alone failed to induce CTLs, in vivo depletion of pDCs impaired CTL-mediated virus eradication. LNDCs from pDC-depleted mice showed impaired cluster formation with T cells and antigen presentation to prime CTLs. Transferring circulating pDC precursors from wild-type, but not CXCR3-deficient, mice to pDC-depleted mice restored CTL induction by impaired LNDCs. In vitro co-culture experiments revealed that pDCs provided help signals that recovered impaired LNDCs in a CD2- and CD40L-dependent manner. pDC-derived IFN-α further stimulated the recovered LNDCs to induce CTLs. Therefore, the help provided by pDCs for LNDCs in primary immune responses seems to be pivotal to optimally inducing anti-HSV CTLs.