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.

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 Activation-induced cell death of self-reactive regulatory T cells drives autoimmunity

2019 ◽  
Vol 116 (52) ◽  
pp. 26788-26797
Author(s):  
Ester Badami ◽  
Olivier N. F. Cexus ◽  
Sonia Quaratino
Keyword(s):  
T Cells ◽  
Cell Death ◽  
Lymph Nodes ◽  
Autoimmune Thyroiditis ◽  
The Self ◽  
Thyroid Peroxidase ◽  
Activation Induced Cell Death ◽  
Self Antigen ◽  
Draining Lymph Nodes

Activation of self-reactive T cells is a major driver to autoimmunity and is suppressed by mechanisms of regulation. In a humanized model of autoimmune thyroiditis, we investigated the mechanism underlying break of tolerance. Here, we found that a human TCR specific for the self-antigen thyroid peroxidase (TPO) is positively selected in the thymus of RAG KO mice on both T effector (Teff) and T regulatory (Treg) CD4+Foxp3+cells. In vivo Teffare present in all immune organs, whereas the TPO-specific Tregare present in all lymphoid organs with the exception of the thyroid-draining lymph nodes. We suggest that the presence of TPO in the thyroid draining lymph nodes induces the activation of Teffand the depletion of Tregvia activation-induced cell death (AICD). Our findings provide insights on the failure of the mechanisms of immune tolerance, with potential implications in designing immunotherapeutic strategies.

scholarly journals Osteopontin Is Involved in the Initiation of Cutaneous Contact Hypersensitivity by Inducing Langerhans and Dendritic Cell Migration to Lymph Nodes

2001 ◽  
Vol 194 (9) ◽  
pp. 1219-1230 ◽  
Author(s):  
J.M. Weiss ◽  
A.C. Renkl ◽  
C.S. Maier ◽  
M. Kimmig ◽  
L. Liaw ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Immune Cells ◽  
Contact Hypersensitivity ◽  
Impaired Ability ◽  
Chemotactic Protein ◽  
Dendritic Cell Migration ◽  
Sensitization Phase ◽  
Deficient Mice ◽  
Draining Lymph Nodes ◽  
Lymphatic Organs

Osteopontin (OPN) is a chemotactic protein that attracts immune cells, to inflammatory sites. The sensitization phase of allergic cutaneous contact hypersensitivity (CHS) requires the migration of Langerhans cells/dendritic cells (LCs/DCs) from skin to draining lymph nodes. Characterizing OPN function for LC/DC migration we found upregulated OPN expression in hapten sensitized skin and draining lymph nodes. OPN induces chemotactic LC/DC migration, initiates their emigration from the epidermis, and attracts LCs/DCs to draining lymph nodes by interacting with CD44 and αv integrin. Furthermore, OPN-deficient mice have a significantly reduced CHS response that correlates with an impaired ability of OPN-deficient mice to attract LCs/DCs to draining lymph nodes. In conclusion, OPN is an important factor in the initiation of CHS by guiding LCs/DCs from skin into lymphatic organs.

scholarly journals Leukocytes Infiltrate the Skin and Draining Lymph Nodes in Response to the ProtozoanLeishmania infantum chagasi

2010 ◽  
Vol 79 (1) ◽  
pp. 108-117 ◽  
Author(s):  
Colin J. Thalhofer ◽  
Yani Chen ◽  
Bayan Sudan ◽  
Laurie Love-Homan ◽  
Mary E. Wilson
Keyword(s):  
Lymph Nodes ◽  
Inflammatory Cells ◽  
Imaging Flow Cytometry ◽  
Intracellular Parasites ◽  
Vector Borne ◽  
Neutrophil Depletion ◽  
And Control ◽  
Second Wave ◽  
Draining Lymph Nodes

ABSTRACTThe vector-borne protozoanLeishmania infantum chagasicauses minimal inflammation after inoculation into skin but disseminates to cause fatal visceral leishmaniasis. To define the inflammatory response at the parasite inoculation site, we introduced metacyclicL. infantum chagasipromastigotes intradermally into BALB/c mouse ears and studied inflammatory cells over 7 days. Ly6G+neutrophils rapidly infiltrated the dermis, peaking after 6 to 24 h. Macrophages and NK cells next infiltrated the dermis, and NK followed by B cells expanded in draining lymph nodes. Parasite-containing phagocytes were tracked with fluorescent mCherry-labeledL. infantum chagasi.Ly6G+neutrophils contained the greatest proportion of intracellular parasites 6 to 24 h after inoculation, whereas dermal macrophages harbored the majority of intracellular parasites after 2 to 7 days. These observations were validated microscopically. Low doses of antibody transiently depleted mice of neutrophils, leaving other cells intact. Combined results ofin vivoimaging, flow cytometry, and quantitative PCR showed that neutrophil depletion slowed the clearance of extracellular (luciferase-positive) promastigotes during the first 24 h after inoculation yet decreased the numbers of leukocytes containing intracellular (mCherry-positive) parasites. From 3 days onward, totalL. infantum chagasi-containing dermal leukocytes and totalL. infantum chagasiparasites in draining lymph nodes were similar in both groups. Nonetheless, a second wave ofL. infantum chagasi-containing neutrophils occurred 7 days after parasite inoculation into neutrophil-depleted mice, corresponding to the time of neutrophil recovery. Thus, neutrophils were recruited to the dermis even late after inoculation, andL. infantum chagasitrafficked through neutrophils in both neutrophil-depleted and control mice, albeit with different kinetics. Recruitment of neutrophils and transient parasite residence in neutrophils may play a role in nonulcerative forms of leishmaniasis.

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