scholarly journals α6 Integrins Are Required for Langerhans Cell Migration from the Epidermis

1997 ◽  
Vol 186 (10) ◽  
pp. 1725-1735 ◽  
Author(s):  
Abigail A. Price ◽  
Marie Cumberbatch ◽  
Ian Kimber ◽  
Ann Ager
Keyword(s):  
Lymph Node ◽  
Lymph Nodes ◽  
Topical Administration ◽  
Integrin Subunit ◽  
Recognition Sequence ◽  
Extracellular Matrix Components ◽  
Skin Explants ◽  
Draining Lymph Nodes

Topical exposure of mice to chemical allergens results in the migration of epidermal Langerhans cells (LCs) from the skin and their accumulation as immunostimulatory dendritic cells (DCs) in draining lymph nodes. Epidermal cell–derived cytokines have been implicated in the maturation and migration of LCs, but the adhesion molecules that regulate LC migration have not been studied. We hypothesized that integrin-mediated interactions with extracellular matrix components of the skin and lymph node may regulate LC/DC migration. We found that α6 integrins and α4 integrins were differentially expressed by epidermal LCs and lymph node DCs. A majority of LCs (70%) expressed the α6 integrin subunit, whereas DCs did not express α6 integrins. In contrast, the α4 integrin subunit was expressed at high levels on DCs but at much lower levels on LCs. The anti-α6 integrin antibody, GoH3, which blocks binding to laminin, completely prevented the spontaneous migration of LCs from skin explants in vitro and the rapid migration of LCs from mouse ear skin induced after intradermal administration of TNF-α in vivo. GoH3 also reduced the accumulation of DCs in draining lymph nodes by a maximum of 70% after topical administration of the chemical allergen oxazolone. LCs remaining in the epidermis in the presence of GoH3 adopted a rounded morphology, rather than the interdigitating appearance typical of LCs in naive skin, suggesting that the cells had detached from neighboring keratinocytes and withdrawn cellular processes in preparation for migration, but were unable to leave the epidermis. The anti-α4 integrin antibody PS/2, which blocks binding to fibronectin, had no effect on LC migration from the epidermis either in vitro or in vivo, or on the accumulation of DCs in draining lymph nodes after oxazolone application. RGD-containing peptides were also without effect on LC migration from skin explants. These results identify an important role for α6 integrins in the migration of LC from the epidermis to the draining lymph node by regulating access across the epidermal basement membrane. In contrast, α4 integrins, or other integrin-dependent interactions with fibronectin that are mediated by the RGD recognition sequence, did not influence LC migration from the epidermis. In addition, α4 integrins did not affect the accumulation of LCs as DCs in draining lymph nodes.

CD44-dependent lymphoma cell dissemination: a cell surface CD44 variant, rather than standard CD44, supports in vitro lymphoma cell rolling on hyaluronic acid substrate and its in vivo accumulation in the peripheral lymph nodes

2001 ◽  
Vol 114 (19) ◽  
pp. 3463-3477
Author(s):  
Shulamit B. Wallach-Dayan ◽  
Valentin Grabovsky ◽  
Jürgen Moll ◽  
Jonathan Sleeman ◽  
Peter Herrlich ◽  
...  
Keyword(s):  
Cell Migration ◽  
Hyaluronic Acid ◽  
Lymph Node ◽  
Cell Surface ◽  
Lymph Nodes ◽  
Local Tumor ◽  
Cd44 Variant ◽  
Peripheral Lymph

Cell motility is an essential element of tumor dissemination, allowing organ infiltration by cancer cells. Using mouse LB lymphoma cells transfected with standard CD44 (CD44s) cDNA (LB-TRs cells) or with the alternatively spliced CD44 variant CD44v4-v10 (CD44v) cDNA (LB-TRv cells), we explored their CD44-dependent cell migration. LB-TRv cells, but not LB-TRs or parental LB cells, bound soluble hyaluronic acid (HA) and other glycosaminoglycans (GAGs), and exclusively formed, under physiological shear force, rolling attachments on HA substrate. Furthermore, LB-TRv cells, but not LB-TRs cells or their parental LB cells, displayed accelerated local tumor formation and enhanced accumulation in the peripheral lymph nodes after s.c. inoculation. The aggressive metastatic behavior of i.v.-injected LB-TRV cells, when compared with that of other LB-transfectants, is attributed to more efficient migration to the lymph nodes, rather than to local growth in the lymph node. Injection of anti-CD44 monoclonal antibody or of the enzyme hyaluronidase also prevented tumor growth in lymph nodes of BALB/c mice inoculated with LB-TRv cells. The enhanced in vitro rolling and enhanced in vivo local tumor growth and lymph node invasion disappeared in LB cells transfected with CD44v cDNA bearing a point mutation at the HA binding site, located at the distal end of the molecule constant region. These findings show that the interaction of cell surface CD44v with HA promotes cell migration both in vitro and in vivo, and they contribute to our understanding of the mechanism of cell trafficking, including tumor spread.

scholarly journals Indigenous enteric eosinophils control DCs to initiate a primary Th2 immune response in vivo

2014 ◽  
Vol 211 (8) ◽  
pp. 1657-1672 ◽  
Author(s):  
Derek K. Chu ◽  
Rodrigo Jimenez-Saiz ◽  
Christopher P. Verschoor ◽  
Tina D. Walker ◽  
Susanna Goncharova ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Eosinophil Peroxidase ◽  
Th2 Immune Response ◽  
Intestinal Immune System ◽  
Eosinophil Activation ◽  
And Migration ◽  
Deficient Mice ◽  
Draining Lymph Nodes

Eosinophils natively inhabit the small intestine, but a functional role for them there has remained elusive. Here, we show that eosinophil-deficient mice were protected from induction of Th2-mediated peanut food allergy and anaphylaxis, and Th2 priming was restored by reconstitution with il4+/+ or il4−/− eosinophils. Eosinophils controlled CD103+ dendritic cell (DC) activation and migration from the intestine to draining lymph nodes, events necessary for Th2 priming. Eosinophil activation in vitro and in vivo led to degranulation of eosinophil peroxidase, a granule protein whose enzymatic activity promoted DC activation in mice and humans in vitro, and intestinal and extraintestinal mouse DC activation and mobilization to lymph nodes in vivo. Further, eosinophil peroxidase enhanced responses to ovalbumin seen after immunization. Thus, eosinophils can be critical contributors to the intestinal immune system, and granule-mediated shaping of DC responses can promote both intestinal and extraintestinal adaptive immunity.

scholarly journals THE X-Y-Z SCHEME OF IMMUNOCYTE MATURATION

1968 ◽  
Vol 127 (2) ◽  
pp. 307-325 ◽  
Author(s):  
Vera S. Byers ◽  
Eli E. Sercarz
Keyword(s):  
Lymph Node ◽  
Antibody Response ◽  
Lymph Nodes ◽  
Large Dose ◽  
Primary Response ◽  
Memory Cells ◽  
Secondary Antibody ◽  
Booster Injection

A set of conditions has been described under which primed rabbit lymph nodes produce a secondary antibody response upon in vivo stimulation with a large dose of antigen, but are subsequently "exhausted;" that is, lymph node cultures prepared at intervals following the booster injection cannot be re-stimulated to display tertiary responses. Rabbits given 100-fold less antigen in the booster inoculum were able to give a tertiary response upon in vitro challenge. The system used permits neither induction nor continuation of a primary response to BSA in vitro. Since it could be demonstrated that no memory cells were generated by the booster injection within the intervals between in vivo injection and culture, the tertiary response in nonexhausted nodes must have been due to residual memory cells which remained untriggered by the in vivo booster injection. The unresponsive state was not caused by antibody feedback. These results are interpreted to mean that a population of memory cells can be exhausted by a supraoptimal dose of antigen, rendering the node temporarily incapable of further response. This implies that long-lived memory is not due to asymmetric division of memory cells. The source and fate of memory cells is discussed with regard to this evidence.

scholarly journals Upregulation of VCAM-1 in lymphatic collectors supports dendritic cell entry and rapid migration to lymph nodes in inflammation

2021 ◽  
Vol 218 (7) ◽  
Author(s):  
Jorge Arasa ◽  
Victor Collado-Diaz ◽  
Ioannis Kritikos ◽  
Jessica Danielly Medina-Sanchez ◽  
Mona Carina Friess ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Lymph Nodes ◽  
Early Time ◽  
Lymph Flow ◽  
Cell Entry ◽  
Dependent Manner ◽  
Β1 Integrins ◽  
Skin Explants ◽  
Draining Lymph Nodes

Dendritic cell (DC) migration to draining lymph nodes (dLNs) is a slow process that is believed to begin with DCs approaching and entering into afferent lymphatic capillaries. From capillaries, DCs slowly crawl into lymphatic collectors, where lymph flow induced by collector contraction supports DC detachment and thereafter rapid, passive transport to dLNs. Performing a transcriptomics analysis of dermal endothelial cells, we found that inflammation induces the degradation of the basement membrane (BM) surrounding lymphatic collectors and preferential up-regulation of the DC trafficking molecule VCAM-1 in collectors. In crawl-in experiments performed in ear skin explants, DCs entered collectors in a CCR7- and β1 integrin–dependent manner. In vivo, loss of β1-integrins in DCs or of VCAM-1 in lymphatic collectors had the greatest impact on DC migration to dLNs at early time points when migration kinetics favor the accumulation of rapidly migrating collector DCs rather than slower capillary DCs. Taken together, our findings identify collector entry as a critical mechanism enabling rapid DC migration to dLNs in inflammation.

scholarly journals Tumor ablation plus co-administration of CpG and saponin adjuvants affects IL-1 production and multifunctional T cell numbers in tumor draining lymph nodes

2020 ◽  
Vol 8 (1) ◽  
pp. e000649
Author(s):  
Tonke K Raaijmakers ◽  
Renske J E van den Bijgaart ◽  
Martijn H den Brok ◽  
Melissa Wassink ◽  
Annemarie de Graaf ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Tumor Ablation ◽  
Polymorphonuclear Neutrophil ◽  
Cell Numbers ◽  
Draining Lymph Nodes

BackgroundTumor ablation techniques, like cryoablation, are successfully used in the clinic to treat tumors. The tumor debris remaining in situ after ablation is a major antigen depot, including neoantigens, which are presented by dendritic cells (DCs) in the draining lymph nodes to induce tumor-specific CD8+T cells. We have previously shown that co-administration of adjuvants is essential to evoke strong in vivo antitumor immunity and the induction of long-term memory. However, which adjuvants most effectively combine with in situ tumor ablation remains unclear.Methods and resultsHere, we show that simultaneous administration of cytidyl guanosyl (CpG) with saponin-based adjuvants following cryoablation affects multifunctional T-cell numbers and interleukin (IL)-1 induced polymorphonuclear neutrophil recruitment in the tumor draining lymph nodes, relative to either adjuvant alone. The combination of CpG and saponin-based adjuvants induces potent DC maturation (mainly CpG-mediated), antigen cross-presentation (mainly saponin-based adjuvant mediated), while excretion of IL-1β by DCs in vitro depends on the presence of both adjuvants. Most strikingly, CpG/saponin-based adjuvant exposed DCs potentiate antigen-specific T-cell proliferation resulting in multipotent T cells with increased capacity to produce interferon (IFN)γ, IL-2 and tumor necrosis factor-α in vitro. Also in vivo the CpG/saponin-based adjuvant combination plus cryoablation increased the numbers of tumor-specific CD8+T cells showing enhanced IFNγ production as compared with single adjuvant treatments.ConclusionsCollectively, these data indicate that co-injection of CpG with saponin-based adjuvants after cryoablation induces an increased amount of tumor-specific multifunctional T cells. The combination of saponin-based adjuvants with toll-like receptor 9 adjuvant CpG in a cryoablative setting therefore represents a promising in situ vaccination strategy.

scholarly journals Immunohistologic and functional characterization of a vascular addressin involved in lymphocyte homing into peripheral lymph nodes.

1988 ◽  
Vol 107 (5) ◽  
pp. 1853-1862 ◽  
Author(s):  
P R Streeter ◽  
B T Rouse ◽  
E C Butcher
Keyword(s):  
Endothelial Cells ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Peyer's Patches ◽  
Peripheral Lymph Node ◽  
Lymphocyte Homing ◽  
Tissue Specific ◽  
Peripheral Lymph

The tissue localization or "homing" of circulating lymphocytes is directed in part by specialized vessels that define sites of lymphocyte exit from the blood. In peripheral lymph nodes, mucosal lymphoid tissues (Peyer's patches and appendix), and sites of chronic inflammation, for example, lymphocytes leave the blood by adhering to and migrating between those endothelial cells lining postcapillary high endothelial venules (HEV). Functional analyses of lymphocyte interactions with HEV have shown the lymphocytes can discriminate between HEV in different tissues, indicating that HEV express tissue-specific determinants or address signals for lymphocyte recognition. We recently described such a tissue-specific "vascular addressin" that is selectively expressed by endothelial cells supporting lymphocyte extravasation into mucosal tissues and that appears to be required for mucosa-specific lymphocyte homing (Streeter, P. R., E. L. Berg, B. N. Rouse, R. F. Bargatze, and E. C. Butcher. 1988. Nature (Lond.). 331:41-46). Here we document the existence and tissue-specific distribution of a distinct HEV differentiation antigen. Defined by monoclonal antibody MECA-79, this antigen is expressed at high levels on the lumenal surface and in the cytoplasm of HEV in peripheral lymph nodes. By contrast, although MECA-79 stains many HEV in the mucosal Peyer's patches, expression in most cases is restricted to the perivascular or ablumenal aspect of these venules. In the small intestine lamina propria, a mucosa-associated site that supports the extravasation of lymphocytes, venules do not stain with MECA-79. Finally, we demonstrate that MECA-79 blocks binding of both normal lymphocytes and a peripheral lymph node-specific lymphoma to peripheral lymph node HEV in vitro and that it also inhibits normal lymphocyte homing to peripheral lymph nodes in vivo without significantly influencing lymphocyte interactions with Peyer's patch HEV in vitro or in vivo. Thus, MECA-79 defines a novel vascular addressin involved in directing lymphocyte homing to peripheral lymph nodes.

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.

scholarly journals CD49b defines functionally mature Treg cells that survey skin and vascular tissues

2018 ◽  
Vol 215 (11) ◽  
pp. 2796-2814 ◽  
Author(s):  
Xiying Fan ◽  
Bruno Moltedo ◽  
Alejandra Mendoza ◽  
Alexey N. Davydov ◽  
Mehlika B. Faire ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Cell Subset ◽  
Treg Cells ◽  
Lymphoid Organs ◽  
Developmental Trajectory ◽  
Peripheral Tissues ◽  
Secondary Lymphoid Organs ◽  
Draining Lymph Nodes

Regulatory T (Treg) cells prevent autoimmunity by limiting immune responses and inflammation in the secondary lymphoid organs and nonlymphoid tissues. While unique subsets of Treg cells have been described in some nonlymphoid tissues, their relationship to Treg cells in secondary lymphoid organs and circulation remains unclear. Furthermore, it is possible that Treg cells from similar tissue types share largely similar properties. We have identified a short-lived effector Treg cell subset that expresses the α2 integrin, CD49b, and exhibits a unique tissue distribution, being abundant in peripheral blood, vasculature, skin, and skin-draining lymph nodes, but uncommon in the intestines and in viscera-draining lymph nodes. CD49b+ Treg cells, which display superior functionality revealed by in vitro and in vivo assays, appear to develop after multiple rounds of cell division and TCR-dependent activation. Accordingly, single-cell RNA-seq analysis placed these cells at the apex of the Treg developmental trajectory. These results shed light on the identity and development of a functionally potent subset of mature effector Treg cells that recirculate through and survey peripheral tissues.

CCR7 is involved in the migration of neutrophils to lymph nodes

Blood ◽  
2011 ◽  
Vol 117 (4) ◽  
pp. 1196-1204 ◽  
Author(s):  
Céline Beauvillain ◽  
Pierre Cunin ◽  
Andrea Doni ◽  
Mari Scotet ◽  
Sébastien Jaillon ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Human Neutrophils ◽  
Interleukin 17 ◽  
Wild Type ◽  
Adaptive Immune ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Draining Lymph Nodes

Abstract Increasing evidence suggests that neutrophils may participate in the regulation of adaptive immune responses, and can reach draining lymph nodes and cross-prime naive T cells. The aim of this study was to identify the mechanism(s) involved in the migration of neutrophils to the draining lymph nodes. We demonstrate that a subpopulation of human and mouse neutrophils express CCR7. CCR7 is rapidly expressed at the membrane upon stimulation. In vitro, stimulated human neutrophils migrate in response to the CCR7 ligands CCL19 and CCL21. In vivo, injection of complete Freund adjuvant induces a rapid recruitment of neutrophils to the lymph nodes in wild-type mice but not in Ccr7−/− mice. Moreover, intradermally injected interleukin-17–and granulocyte-macrophage colony-stimulating factor–stimulated neutrophils from wild-type mice, but not from Ccr7−/− mice, migrate to the draining lymph nodes. These results identify CCR7 as a chemokine receptor involved in the migration of neutrophils to the lymph nodes.

Sign in / Sign up

Export Citation Format

Share Document