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.

Tissue inflammation modulates gene expression of lymphatic endothelial cells and dendritic cell migration in a stimulus-dependent manner

Blood ◽  
2011 ◽  
Vol 118 (1) ◽  
pp. 205-215 ◽  
Author(s):  
Benjamin Vigl ◽  
David Aebischer ◽  
Maximilian Nitschké ◽  
Maria Iolyeva ◽  
Tamara Röthlin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Dendritic Cell ◽  
Lymph Nodes ◽  
Adhesion Molecules ◽  
Contact Hypersensitivity ◽  
Dependent Manner ◽  
Lymphatic Endothelial Cells ◽  
Tissue Inflammation ◽  
Draining Lymph Nodes

Abstract Chemokines and adhesion molecules up-regulated in lymphatic endothelial cells (LECs) during tissue inflammation are thought to enhance dendritic cell (DC) migration to draining lymph nodes, but the in vivo control of this process is not well understood. We performed a transcriptional profiling analysis of LECs isolated from murine skin and found that inflammation induced by a contact hypersensitivity (CHS) response up-regulated the adhesion molecules ICAM-1 and VCAM-1 and inflammatory chemokines. Importantly, the lymphatic markers Prox-1, VEGFR3, and LYVE-1 were significantly down-regulated during CHS. By contrast, skin inflammation induced by complete Freund adjuvant induced a different pattern of chemokine and lymphatic marker gene expression and almost no ICAM-1 up-regulation in LECs. Fluorescein isothiocyanate painting experiments revealed that DC migration to draining lymph nodes was more strongly increased in complete Freund adjuvant-induced than in CHS-induced inflammation. Surprisingly, DC migration did not correlate with the induction of CCL21 and ICAM-1 protein in LECs. Although the requirement for CCR7 signaling became further pronounced during inflammation, CCR7-independent signals had an additional, albeit moderate, impact on enhancing DC migration. Collectively, these findings indicate that DC migration in response to inflammation is stimulus-specific, mainly CCR7-dependent, and overall only moderately enhanced by LEC-induced genes other than CCL21.

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.

scholarly journals In vivo magnetic resonance imaging of dendritic cell migration into the draining lymph nodes of mice

2006 ◽  
Vol 36 (9) ◽  
pp. 2544-2555 ◽  
Author(s):  
Dirk Baumjohann ◽  
Andreas Hess ◽  
Lubos Budinsky ◽  
Kay Brune ◽  
Gerold Schuler ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Cell Migration ◽  
Dendritic Cell ◽  
Magnetic Resonance ◽  
Lymph Nodes ◽  
Resonance Imaging ◽  
Dendritic Cell Migration ◽  
Draining Lymph Nodes

scholarly journals In vivo two-photon imaging of T cell motility in joint-draining lymph nodes in a mouse model of rheumatoid arthritis

2012 ◽  
Vol 278 (1-2) ◽  
pp. 158-165 ◽  
Author(s):  
Tamás Kobezda ◽  
Sheida Ghassemi-Nejad ◽  
Tibor T. Glant ◽  
Katalin Mikecz
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
Mouse Model ◽  
Lymph Nodes ◽  
Cell Motility ◽  
Two Photon ◽  
Photon Imaging ◽  
Two Photon Imaging ◽  
Draining Lymph Nodes

scholarly journals Altered ratio of dendritic cell subsets in skin-draining lymph nodes promotes Th2-driven contact hypersensitivity

2021 ◽  
Vol 118 (3) ◽  
pp. e2021364118
Author(s):  
Hannah L. Miller ◽  
Prabhakar Sairam Andhey ◽  
Melissa K. Swiecki ◽  
Bruce A. Rosa ◽  
Konstantin Zaitsev ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Lymph Nodes ◽  
Diphtheria Toxin ◽  
Fluorescein Isothiocyanate ◽  
Skin Inflammation ◽  
Contact Hypersensitivity ◽  
Type I ◽  
Th2 Response ◽  
Draining Lymph Nodes

Plasmacytoid dendritic cells (pDCs) specialize in the production of type I IFN (IFN-I). pDCs can be depleted in vivo by injecting diphtheria toxin (DT) in a mouse in which pDCs express a diphtheria toxin receptor (DTR) transgene driven by the human CLEC4C promoter. This promoter is enriched for binding sites for TCF4, a transcription factor that promotes pDC differentiation and expression of pDC markers, including CLEC4C. Here, we found that injection of DT in CLEC4C-DTR+ mice markedly augmented Th2-dependent skin inflammation in a model of contact hypersensitivity (CHS) induced by the hapten fluorescein isothiocyanate. Unexpectedly, this biased Th2 response was independent of reduced IFN-I accompanying pDC depletion. In fact, DT treatment altered the representation of conventional dendritic cells (cDCs) in the skin-draining lymph nodes during the sensitization phase of CHS; there were fewer Th1-priming CD326+ CD103+ cDC1 and more Th2-priming CD11b+ cDC2. Single-cell RNA-sequencing of CLEC4C-DTR+ cDCs revealed that CD326+ DCs, like pDCs, expressed DTR and were depleted together with pDCs by DT treatment. Since CD326+ DCs did not express Tcf4, DTR expression might be driven by yet-undefined transcription factors activating the CLEC4C promoter. These results demonstrate that altered DC representation in the skin-draining lymph nodes during sensitization to allergens can cause Th2-driven CHS.

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 PGE2-induced metalloproteinase-9 is essential for dendritic cell migration

Blood ◽  
2008 ◽  
Vol 111 (1) ◽  
pp. 260-270 ◽  
Author(s):  
Jui-Hung Yen ◽  
Tanzilya Khayrullina ◽  
Doina Ganea
Keyword(s):  
Lymph Nodes ◽  
Basement Membranes ◽  
Directional Migration ◽  
Dendritic Cell Migration ◽  
Membrane Bound ◽  
Induced Changes ◽  
Expression Program ◽  
Metalloproteinase 9 ◽  
Draining Lymph Nodes

Following antigen acquisition and maturation, dendritic cells (DCs) disengage from the extracellular matrix, cross basement membranes, and travel to draining lymph nodes to activate T cells. CCR7 expression is necessary but not sufficient for the directional migration of DCs. Prostaglandin E2 (PGE2), present in inflammatory sites, induces DC migration, presumably by enacting a migration-permissive gene expression program. Since regulation of DC migration is highly important for their use in vaccination and therapy, we examined the PGE2-induced changes in the expression of metalloproteinases (MMPs). Our results indicate that PGE2 significantly up-regulates MMP-9 expression, induces both secreted and membrane-bound MMP-9, and that in turn, DC-derived MMP-9 is essential for DC chemotaxis in response to the CCR7 ligand CCL19, Matrigel migration, and in vivo migration in both wild-type and MMP-9–deficient hosts. We conclude that DCs matured within inflammatory sites require both CCR7 and PGE2-induced MMP-9 for their directional migration to draining lymph nodes.

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