Subcapsular Sinus Macrophages: The Seat of Innate and Adaptive Memory in Murine Lymph Nodes

2019 ◽  
Vol 40 (1) ◽  
pp. 35-48 ◽  
Author(s):  
Imogen Moran ◽  
Abigail K. Grootveld ◽  
Akira Nguyen ◽  
Tri Giang Phan
Keyword(s):  
Lymph Nodes ◽  
Adaptive Memory ◽  
Subcapsular Sinus

scholarly journals Single-Cell Transcriptional Heterogeneity of Lymphatic Endothelial Cells in Normal and Inflamed Murine Lymph Nodes

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1371
Author(s):  
Eliane Sibler ◽  
Yuliang He ◽  
Luca Ducoli ◽  
Nadja Keller ◽  
Noriki Fujimoto ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Lymph Nodes ◽  
Single Cell ◽  
In Silico Analysis ◽  
Skin Inflammation ◽  
Lymphatic Endothelial Cells ◽  
Depth Analysis ◽  
Subcapsular Sinus ◽  
Transcriptional Changes ◽  
Sinus Floor

The lymphatic system plays a crucial role in immunity and lymph nodes (LNs) undergo drastic remodeling during inflammation. Here, we used single-cell RNA sequencing to investigate transcriptional changes in lymphatic endothelial cells (LECs) in LNs draining naïve and inflamed skin. We found that subsets of LECs lining the different LN sinuses responded individually to skin inflammation, suggesting that they exert distinct functions under pathological conditions. Among the genes dysregulated during inflammation, we confirmed an up-regulation of CD200 in the LECs lining the subcapsular sinus floor with a possible function in immune regulation. Furthermore, by in silico analysis, we predicted numerous possible interactions of LECs with diverse immune cells in the LNs and found similarities in the transcriptional changes of LN LECs in different skin inflammation settings. In summary, we provide an in-depth analysis of the transcriptional landscape of LN LECs in the naïve state and in skin inflammation.

scholarly journals Fc chimeric protein containing the cysteine-rich domain of the murine mannose receptor binds to macrophages from splenic marginal zone and lymph node subcapsular sinus and to germinal centers.

1996 ◽  
Vol 184 (5) ◽  
pp. 1927-1937 ◽  
Author(s):  
L Martínez-Pomares ◽  
M Kosco-Vilbois ◽  
E Darley ◽  
P Tree ◽  
S Herren ◽  
...  
Keyword(s):  
Lymph Node ◽  
Lymph Nodes ◽  
B Cell ◽  
Marginal Zone ◽  
Chimeric Protein ◽  
Mannose Receptor ◽  
Germinal Centers ◽  
White Pulp ◽  
Subcapsular Sinus ◽  
Splenic White Pulp

Ligands for the cysteine-rich (CR) domain of the mannose receptor (MR) were detected by incubating murine tissues with a chimeric protein containing CR fused to the Fc region of human IgG1 (CR-Fc). In naive mice, CR-Fc bound to sialoadhesin+, F4/80low/-, macrosialin+ macrophages (M phi) in spleen marginal zone (metallophilic M phi) and lymph node subcapsular sinus. Labeling was also observed in B cell areas of splenic white pulp. Western blotting analysis of spleen and lymph nodes lysates revealed a restricted number of molecules that interacted specifically with CR-Fc. In immunized mice, labeling was upregulated on germinal centers in splenic white pulp and follicular areas of lymph nodes. Kinetic analysis of the pattern of CR-Fc labeling in lymph nodes during a secondary immune response to ovalbumin showed that CR ligand expression migrated towards B cell areas, associated with cells displaying distinctive dendritic morphology, and accumulated in developing germinal centers. These studies suggest that MR+ cells or MR-carbohydrate-containing antigen complexes could be directed towards areas where humoral immune responses take place, through the interaction of the MR CR domain with molecules expressed in specialized macrophage populations and antigen transporting cells.

scholarly journals Single-cell mapping reveals new markers and functions of lymphatic endothelial cells in lymph nodes

2020 ◽  
Author(s):  
Noriki Fujimoto ◽  
Yuliang He ◽  
Marco D’Addio ◽  
Carlotta Tacconi ◽  
Michael Detmar ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Immune Responses ◽  
Lymph Nodes ◽  
Single Cell ◽  
Cancer Metastasis ◽  
Lymphatic Vessels ◽  
Peripheral Tolerance ◽  
Lymphatic Endothelial Cells ◽  
Subcapsular Sinus ◽  
Lymphocyte Egress

ABSTRACTLymph nodes (LNs) are highly organized secondary lymphoid organs that mediate adaptive immune responses to antigens delivered via afferent lymphatic vessels. Lymphatic endothelial cells (LECs) line intranodal lymphatic sinuses and organize lymph and antigen distribution. LECs also directly regulate T cells, mediating peripheral tolerance to self-antigens, and play a major role in many diseases including cancer metastasis. However, little is known about the phenotypic and functional heterogeneity of LN LECs. Using single-cell RNA sequencing, we comprehensively defined the transcriptome of LECs in murine skin-draining LNs, and identified new markers and functions of distinct LEC subpopulations. We found that LECs residing in the subcapsular sinus have an unanticipated function in scavenging of modified LDL and also identified a specific cortical LEC subtype implicated in rapid lymphocyte egress from LNs. Our data provide new insights into the diversity of LECs in murine lymph nodes and a rich resource for future studies into the regulation of immune responses by lymph node LECs.

scholarly journals CELLULAR MECHANISMS OF ANTIBACTERIAL DEFENSE IN LYMPH NODES

1949 ◽  
Vol 90 (6) ◽  
pp. 567-576 ◽  
Author(s):  
Ralph O. Smith ◽  
W. Barry Wood
Keyword(s):  
Lymph Node ◽  
Lymph Nodes ◽  
Blood Vessels ◽  
The Other ◽  
Polymorphonuclear Leucocytes ◽  
Cellular Mechanisms ◽  
Inflammatory Focus ◽  
Subcapsular Sinus ◽  
Infected Lymph Node ◽  
Leucocyte Infiltration

The origin of the polymorphonuclear leucocytes found in the intermediary and subcapsular sinuses of the popliteal lymph node during acute bacterial lymphadenitis, and the effect of this leucocyte infiltration on the passage of bacteria through the lymph node have been investigated. It has been demonstrated that: 1. The polymorphonuclear leucocytes in the nodal sinuses originate both from blood vessels of the lymph node and from the primary inflammatory focus in the tissues. 2. Granulocytes invading the intermediary sinuses of the infected lymph node arise primarily from capillaries lining these sinuses. 3. Most of the polymorphonuclear leucocytes in the subcapsular sinus, on the other hand, originate from the inflammatory focus in the tissues and appear to traverse the node by way of this peripheral sinus. 4. The bacteremia following direct intralymphatic injection of pneumococci is suppressed by the presence of preformed inflammatory exudate in the nodal sinuses indicating that the filtering capacity of the node is thereby greatly increased.

Subcapsular sinus macrophages in lymph nodes clear lymph-borne viruses and present them to antiviral B cells

Nature ◽  
2007 ◽  
Vol 450 (7166) ◽  
pp. 110-114 ◽  
Author(s):  
Tobias Junt ◽  
E. Ashley Moseman ◽  
Matteo Iannacone ◽  
Steffen Massberg ◽  
Philipp A. Lang ◽  
...  
Keyword(s):  
B Cells ◽  
Lymph Nodes ◽  
Subcapsular Sinus

scholarly journals Spatially regulated protease activity in lymph nodes renders B cell follicles a sanctuary for retention of intact antigens

2021 ◽  
Author(s):  
Aereas Aung ◽  
Ang Cui ◽  
Ava P Soleimany ◽  
Maurice Bukenya ◽  
Heya Lee ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
B Cell ◽  
Protease Activity ◽  
Structural Integrity ◽  
Follicular Dendritic Cell ◽  
Cell Responses ◽  
Degradation Rates ◽  
Subcapsular Sinus ◽  
Protein Immunization

The structural integrity of vaccine antigens is critical, because antigen breakdown in vivo could eliminate neutralizing epitopes and create competing B cell responses against irrelevant breakdown products. Using FRET imaging and imaging zymography, we found that protease activity and antigen breakdown are spatially heterogeneous in lymph nodes. Following protein immunization, antigens are rapidly degraded in the subcapsular sinus, paracortex, and interfollicular regions of the tissue. By contrast, the follicles and follicular dendritic cell (FDC) networks exhibit low protease activity and antigen degradation rates. Immunization regimens targeting antigen rapidly to FDCs led to germinal centers (GCs) where responses to intact antigen were highly dominant, while traditional bolus immunizations led to weaker GC responses where more GC B cells bound to breakdown products than intact antigen. Thus, spatially-compartmentalized antigen proteolysis impacts humoral immunity and can be exploited to enhance vaccine-induced production of antibody responses against key pathogen structural epitopes.

scholarly journals Lymph-Derived Neutrophils Primarily Locate to the Subcapsular and Medullary Sinuses in Resting and Inflamed Lymph Nodes

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1486
Author(s):  
Jenny de Castro de Castro Pinho ◽  
Reinhold Förster
Keyword(s):  
Lymph Node ◽  
Lymph Nodes ◽  
Tissue Injury ◽  
Lymphatic Vessels ◽  
Functional Behavior ◽  
Subcapsular Sinus ◽  
Activated Neutrophils ◽  
Tissue Site

Neutrophils are the first immune cells to be recruited from the blood to the tissue site of an infection or inflammation. It has been suggested that neutrophils are capable of migrating from the infected tissue via lymphatic vessels to the draining lymph nodes. However, it remains elusive as to which areas within the lymph nodes can be reached by such reversely migrating cells. To address this question, we applied a model for adoptive neutrophil transfer into the afferent lymphatic vessel that drains towards the popliteal lymph node in mice. We showed that resting and in vitro-activated neutrophils did not enter the lymph node parenchyma but localized primarily in the subcapsular and medullary sinuses. Within the medulla, neutrophils show random migration and are able to sense laser-induced sterile tissue injury by massively swarming to the damaged tissue site. Co-injected dendritic cells supported the entry of resting neutrophils into the lymph node parenchyma via the subcapsular sinus. In contrast, in vivo-activated adoptively transferred neutrophils were capable of migrating into the interfollicular areas of the lymph node. Collectively, the data presented here give further insights into the functional behavior of neutrophils within the lymph nodes.

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