scholarly journals Pre‐incubation of corneal donor tissue with sCD83 improves graft survival via the induction of alternatively activated macrophages and tolerogenic dendritic cells

2021 ◽  
Author(s):  
Katrin Peckert‐Maier ◽  
Alfrun Schönberg ◽  
Andreas B. Wild ◽  
Dmytro Royzman ◽  
Gabriele Braun ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Graft Survival ◽  
Activated Macrophages ◽  
Alternatively Activated Macrophages ◽  
Donor Tissue ◽  
Tolerogenic Dendritic Cells ◽  
Alternatively Activated ◽  
Corneal Donor ◽  
Corneal Donor Tissue

Preincubation of donor tissue with a VEGF cytokine trap promotes subsequent high-risk corneal transplant survival

2021 ◽  
pp. bjophthalmol-2021-319745
Author(s):  
Wei Zhang ◽  
Alfrun Schönberg ◽  
Matthias Hamdorf ◽  
Tihomir Georgiev ◽  
Claus Cursiefen ◽  
...  
Keyword(s):  
High Risk ◽  
Graft Survival ◽  
Corneal Transplantation ◽  
Corneal Transplant ◽  
Post Transplantation ◽  
Human Igg ◽  
Transplant Survival ◽  
Donor Tissue ◽  
Corneal Donor ◽  
Corneal Donor Tissue

AimsPathological neovascularisation of the host bed and the transplant itself is the main risk factor for graft rejection after corneal transplantation. This study aims to prevent this process by preincubation of the corneal donor tissue ex vivo with an antivascular endothelial growth factor (VEGF) cytokine trap blocking additional postsurgical hemangiogenesis and lymphangiogenesis to promote high-risk graft survival.MethodsThe donor tissue was preincubated with a VEGFR1R2 cytokine trap for 24 hours prior to murine high-risk corneal transplantation (human IgG Fc was used as the control). The distribution of VEGFR1R2 Trap in the cornea was investigated by immunohistochemistry. Corneas were excised to quantify the blood vessels (BVs) and lymphatic vessels (LVs) and draining lymph nodes (dLNs) were harvested to analyse the phenotype of dendritic cells (DCs) and T cells at week 1, 2 and 8 post-transplantation. Graft survival was compared between preincubation with VEGFR1R2 Trap and human IgG Fc in high-risk recipients.ResultsVEGFR1R2 Trap was present in the graft for at least 2 weeks after surgery and additionally diffused into the corneal recipient. BVs, LVs and macrophages in the whole cornea were significantly decreased 1-week and 2-week post-transplantation (p<0.05). In dLNs the frequency of CD11c+DCs was significantly reduced, whereas CD200R+ regulatory DCs were significantly increased after keratoplasty (p<0.05). Furthermore, long-term high-risk graft survival was significantly improved (p<0.01).ConclusionsPreincubation of corneal donor tissue with a VEGFR1R2 cytokine trap can significantly promote subsequent high-risk corneal transplant survival and thereby opens new treatment avenues for high-risk corneal transplantation.

scholarly journals A phased strategy to differentiate human CD14+monocytes into classically and alternatively activated macrophages and dendritic cells

BioTechniques ◽  
2016 ◽  
Vol 61 (1) ◽  
Author(s):  
Jelani C. Zarif ◽  
James R. Hernandez ◽  
James E. Verdone ◽  
Scott P. Campbell ◽  
Charles G. Drake ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Activated Macrophages ◽  
Alternatively Activated Macrophages ◽  
Alternatively Activated

scholarly journals P063 The immunological landscape of intestinal fibrosis in Crohn’s Disease

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S168-S169
Author(s):  
I Jacobs ◽  
B Creyns ◽  
G Dragoni ◽  
J Cremer ◽  
G Bislenghi ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Immune Cells ◽  
Flow Cytometric Analysis ◽  
Rank Test ◽  
Activated Macrophages ◽  
Alternatively Activated Macrophages ◽  
Fibrotic Tissue ◽  
Alternatively Activated

Abstract Background Patients with Crohn’s disease (CD) often develop strictures, necessitating surgical intervention. The immune pathways expressed in the fibrotic regions, especially in the deeper intestinal layers, are poorly characterized hence hampering therapeutic development for anti-fibrotic agents. We performed a detailed analysis of the immune cell populations in both inflammation and fibrosis in the mucosa and deeper intestinal layers in CD patients. Methods Patients with stricturing CD (n=25) or colorectal cancer (CRC, n=10), undergoing ileocolonic resection were included. The resection specimen of CD patients was macroscopically subdivided into fibrotic, inflammatory but not fibrotic, and unaffected regions by an IBD-experienced histopathologist. The mucosal layer was furthermore separated from the deeper intestinal layers. Immune cells were isolated, followed by flow cytometry. Quantitative real time PCR (qRT-PCR) was performed for the eosinophil chemoattractant CCL11 coding for eotaxin-1 and normalized against the housekeeping genes RPL13a and PPIA. Wilcoxon matched-pairs sign rank test was performed on paired samples while Dunn’s multiple testing was performed for unpaired comparisons. Results Flow cytometric analysis in CD patients showed mainly B cell enrichment in fibrotic tissue compared to the unaffected tissue, both in the mucosa (30.2% vs 20.9% of CD45+ cells, p=0.001) as in deeper layers (34.4% vs 24.1% of CD45+ cells, p=0.01) (figure 1). Mature dendritic cells (mDC), alternatively-activated macrophages and eosinophils were also enriched but in the deeper layers of the fibrotic segment compared to the mucosa (4.3% vs 3.4%, 1.07% vs 0.04% and 2.3% vs 1.5% of CD45+ cells; p = 0.02, 0.008 and 0.02) (figure 2). Moreover, increased eosinophilic presence was also shown in the unaffected CD region compared to the fibrotic area, both in deeper layers (4.0% vs 2.3% of CD45+ cells; p=0.03) as the mucosa (2.4% vs 1.5% of CD45+ cells; p=0.01) as well as in the inflamed deeper layers compared to the superficial layers (3.3% vs 2.1% of CD45+ cells, p=0.04). These data were corroborated by increased CCL11 mRNA expression, in the deeper layers of fibrotic tissue compared to the mucosa (52.3% vs 31.0%, p=0.03). Conclusion Our results suggest a role for innate immune cells in CD complicated with fibrosis. Especially in the deeper layers, eosinophils, mature dendritic cells and alternatively-activated macrophages are implicated. The eosinophilic enrichment in the deeper layers may partly be attributed to an increased eosinophil recruitment by CCL11. Our results offer opportunities for anti-fibrotic drug development in CD.

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