Su.13. Pancreatic Lymph Nodes of Prediabetic Nod Mice Preferentially Attract Dendritic Cells: Effects of Local Delivery of Il-4 By Lentivirally Transduced Dendritic Cells

2006 ◽  
Vol 119 ◽  
pp. S164
Author(s):  
Remi Creusot ◽  
Shahriar Yaghoubi ◽  
Demi Dang ◽  
Karine Breckpot ◽  
Kris Thielemans ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Lymph Nodes ◽  
Nod Mice ◽  
Local Delivery ◽  
Pancreatic Lymph Nodes

Activation of aryl hydrocarbon receptor by TCDD prevents diabetes in NOD mice and increases Foxp3+ T cells in pancreatic lymph nodes

Immunotherapy ◽  
2009 ◽  
Vol 1 (4) ◽  
pp. 539-547
Author(s):  
Nancy I Kerkvliet ◽  
Linda B Steppan ◽  
William Vorachek ◽  
Shannon Oda ◽  
David Farrer ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Aryl Hydrocarbon Receptor ◽  
T Cell Activation ◽  
Cell Activation ◽  
Autoimmune Encephalitis ◽  
Nod Mice ◽  
Aryl Hydrocarbon ◽  
Immune Mediated ◽  
Tcdd Treatment ◽  
Pancreatic Lymph Nodes

The ligand-activated transcription factor, aryl hydrocarbon receptor (AHR), is a novel inducer of adaptive Tregs. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), the most potent AHR ligand, induces adaptive CD4+CD25+ Tregs during an acute graft-versus-host (GvH) response and prevents the generation of allospecific cytotoxic T lymphocytes. TCDD also suppresses the induction of experimental autoimmune encephalitis in association with an expanded population of Foxp3+ Tregs. In this study, we show that chronic treatment of NOD mice with TCDD potently suppresses the development of autoimmune Type 1 diabetes in parallel with greatly reduced pancreatic islet insulitis and an expanded population of CD4+CD25+Foxp3+ cells in the pancreatic lymph nodes. When treatment with TCDD was terminated after 15 weeks (23 weeks of age), mice developed diabetes over the next 8 weeks in association with lower numbers of Tregs and decreased activation of AHR. Analysis of the expression levels of several genes associated with inflammation, T-cell activation and/or Treg function in pancreatic lymph node cells failed to reveal any differences associated with TCDD treatment. Taken together, the data suggest that AHR activation by TCDD-like ligands may represent a novel avenue for treatment of immune-mediated diseases.

scholarly journals Activated NKT Cells Inhibit Autoimmune Diabetes through Tolerogenic Recruitment of Dendritic Cells to Pancreatic Lymph Nodes

2005 ◽  
Vol 174 (3) ◽  
pp. 1196-1204 ◽  
Author(s):  
Yi-Guang Chen ◽  
Caroline-Morgane Choisy-Rossi ◽  
Thomas M. Holl ◽  
Harold D. Chapman ◽  
Gurdyal S. Besra ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Lymph Nodes ◽  
Autoimmune Diabetes ◽  
Nkt Cells ◽  
Pancreatic Lymph Nodes

scholarly journals Pancreatic Lymph Nodes Are Required for Priming of β Cell Reactive T Cells in NOD Mice

2002 ◽  
Vol 196 (3) ◽  
pp. 369-377 ◽  
Author(s):  
Marie-Claude Gagnerault ◽  
Jian Jian Luan ◽  
Chantal Lotton ◽  
Françoise Lepault
Keyword(s):  
T Cells ◽  
Lymph Nodes ◽  
Autoimmune Diabetes ◽  
Adult Life ◽  
Nod Mice ◽  
Autoreactive T Cells ◽  
Nonobese Diabetic ◽  
Autoreactive T Cell ◽  
Pancreatic Lymph Nodes ◽  
Diabetes Development

Nonobese diabetic (NOD) mice develop spontaneous autoimmune diabetes that results from the destruction of insulin secreting β cells by diabetogenic T cells. The time and location of the encounter of autoantigen(s) by naive autoreactive T cells in normal NOD mice are still elusive. To address these issues, we analyzed diabetes development in mice whose spleen or pancreatic lymph nodes (panLNs) had been removed. Excision of panLNs (panLNx) at 3 wk protected mice against insulin autoantibodies (IAAs), insulitis, and diabetes development almost completely, but had no effect when performed at 10 wk. The protection afforded by panLNx at weaning was not due to modifications of the immune system, the absence of autoreactive T cells, or the increase in the potency of regulatory T cells. That panLNs are dispensable during adult life was confirmed by the capacity of 10-wk-old panLNx irradiated recipients to develop diabetes upon transfer of diabetogenic T cells. In contrast, splenectomy had no effect at any age. Partial excision of mesenteric LN at 3 wk did not prevent accelerated diabetes by cyclophosphamide as panLNx did. Thus, in normal NOD mice, autoreactive T cell initial priming occurs in LNs draining the target organ of the disease from 3 wk of age.

scholarly journals Administration of Human Derived Upper gut Commensal Prevotella histicola delays the onset of type 1 diabetes in NOD mice

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Eric Marietta ◽  
Irina Horwath ◽  
Stephanie Meyer ◽  
Shahryar Khaleghi-Rostamkolaei ◽  
Eric Norman ◽  
...  
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Regulatory T Cells ◽  
Lymph Nodes ◽  
Nod Mice ◽  
Histopathological Analysis ◽  
Microbial Composition ◽  
Time Points ◽  
Pancreatic Lymph Nodes

Abstract Background Type 1 diabetes (T1D) is an autoimmune disease that is increasing in prevalence worldwide. One of the contributing factors to the pathogenesis of T1D is the composition of the intestinal microbiota, as has been demonstrated. in T1D patients, with some studies demonstrating a deficiency in their levels of Prevotella. We have isolated a strain of Prevotella histicola from a duodenal biopsy that has anti-inflammatory properties, and in addition, alters the development of autoimmune diseases in mouse models. Therefore, our hypothesis is that the oral administration of P. histicola might delay the development of T1D in the non-obese diabetic (NOD) mice. To assess this, we used the following materials and methods. Female NOD mice (ages 5–8 weeks) were administered every other day P. histicola that was cultured in-house. Blood glucose levels were measured every other week. Mice were sacrificed at various time points for histopathological analysis of the pancreas. Modulation of immune response by the commensal was tested by analyzing regulatory T-cells and NKp46+ cells using flow cytometry and intestinal cytokine mRNA transcript levels using quantitative RT-PCR. For microbial composition, 16 s rRNA gene analysis was conducted on stool samples collected at various time points. Results Administration of P. histicola in NOD mice delayed the onset of T1D. Beta diversity in the fecal microbiomes demonstrated that the microbial composition of the mice administered P. histicola was different from those that were not treated. Treatment with P. histicola led to a significant increase in regulatory T cells with a concomitant decrease in NKp46+ cells in the pancreatic lymph nodes as compared to the untreated group after 5 weeks of treatment. Conclusions These observations suggest that P. histicola treatment delayed onset of diabetes by increasing the levels of regulatory T cells in the pancreatic lymph nodes. This preliminary work supports the rationale that enteral exposure to a non pathogenic commensal P. histicola be tested as a future therapy for T1D.

Upregulating CD4+CD25+FOXP3+ Regulatory T Cells in Pancreatic Lymph Nodes in Diabetic NOD Mice by Adjuvant Immunotherapy

2009 ◽  
Vol 87 (2) ◽  
pp. 198-206 ◽  
Author(s):  
Bole Tian ◽  
Jianqiang Hao ◽  
Yu Zhang ◽  
Lei Tian ◽  
Huimin Yi ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Lymph Nodes ◽  
Nod Mice ◽  
Adjuvant Immunotherapy ◽  
Pancreatic Lymph Nodes

Erratum to “TCR repertoire dynamics in the pancreatic lymph nodes of non-obese diabetic (NOD) mice at the time of disease initiation” [Mol. Immunol. 45 (2008) 3059–3064]

2008 ◽  
Vol 45 (14) ◽  
pp. 3863
Author(s):  
Jelena Petrovic Berglund ◽  
Encarnita Mariotti-Ferrandiz ◽  
Eleftheria Rosmaraki ◽  
Håkan Hall ◽  
Pierre-André Cazenave ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Nod Mice ◽  
Tcr Repertoire ◽  
Pancreatic Lymph Nodes ◽  
Disease Initiation

TCR repertoire dynamics in the pancreatic lymph nodes of non-obese diabetic (NOD) mice at the time of disease initiation

2008 ◽  
Vol 45 (11) ◽  
pp. 3059-3064 ◽  
Author(s):  
Jelena Petrovc Berglund ◽  
Encarnita Mariotti-Ferrandiz ◽  
Eleftheria Rosmaraki ◽  
Håkan Hall ◽  
Pierre-André Cazenave ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Nod Mice ◽  
Tcr Repertoire ◽  
Pancreatic Lymph Nodes ◽  
Disease Initiation

scholarly journals Abnormal Cannabidiol protects pancreatic beta cells in mouse models of experimental Type 1 diabetes

2020 ◽  
Author(s):  
Isabel Gonzalez-Mariscal ◽  
Macarena Pozo Morales ◽  
Silvana Yanina Romero-Zerbo ◽  
Vanesa Espinosa-Jimenez ◽  
Alejandro Escamilla ◽  
...  
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Lymph Nodes ◽  
Beta Cell ◽  
Mouse Models ◽  
Nod Mice ◽  
List Type ◽  
Pancreatic Lymph Nodes ◽  
Islet Inflammation

ABSTRACTBackground and PurposeThe atypical cannabinoid Abn-CBD was reported to improve the inflammatory status in preclinical models of several pathologies including autoimmune diseases. However, its potential for autoimmune diabetes, i.e. type 1 diabetes (T1D), is unknown.Experimental ApproachWe used two mouse models of T1D, streptozotocin (STZ)-injected and non-obese diabetic (NOD) mice. Eight-to-ten-week-old male C57Bl6/J mice were pre-treated with Abn-CBD (1mg/kg of body weight) or vehicle for 1 week, following STZ treatment, and euthanized 1 week later. Six-week-old female NOD mice were treated with Abn-CBD (0.1-1mg/kg) or vehicle for 12 weeks and then euthanized. Blood, pancreas, pancreatic lymph nodes and circulating T cells were collected and processed for analysis. Glycemia was also monitored.Key ResultsAbn-CBD decreased circulating proinflammatory cytokines, ameliorated islet inflammation and the autoimmune attack, showing a 2-fold decrease in CD8+ T cells infiltration and reduced Th1/Th2 ratio in pancreatic lymph nodes of STZ-injected mice. Mechanistically, Abn-CBD reduced intra-islet phospho-NF-κB and TXNIP. Concomitant reduction of islet cell apoptosis and intra-islet fibrosis were observed in Abn-CBD pre-treated mice compared to vehicle. In NOD mice, Abn-CBD reduced the expression of Ifng, Il21, Tnfa and Il10 while increased Il4 in circulating CD4+ T cells compared to vehicle, reducing the severity of insulitis and improving glucose tolerance.Conclusion and ImplicationsAltogether, we found that Abn-CBD reduces intra-islet inflammation and delays the progression of insulitis in mouse models of T1D, preserving healthy functional islets. Hence, Abn-CBD and related compounds emerge as new candidates to develop pharmacological strategies to treat early stages of T1D.WHAT IS ALREADY KNOWN-Phytocannabinoids such as cannabidiol (CBD) have anti-inflammatory and glucose-lowering properties-The CBD derivative Abn-CBD ameliorates inflammation in various diseases and modulates beta cell functionWHAT THIS STUDY ADDS-Abn-CBD reduces systemic and pancreatic inflammation in mice models of type 1 diabetes-Abn-CBD prevents beta cell damage and loss during type 1 diabetes onsetCLINICAL SIGNIFICANCE-Synthetic cannabinoids emerge as potential treatment for type 1 diabetes

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