Prominent Lymphatic Vessel Hyperplasia with Progressive Dysfunction and Distinct Immune Cell Infiltration in Lymphedema

Hypertension (HTN) is associated with reduced fertility in men. Although numerous studies report that HTN disrupts hormonal balance in men, less is known about the direct effect of HTN on testes and how HTN influences testicular inflammation and lymphatics. We hypothesized that HTN increases testicular lymphatic vessel density and this is associated with immune cell infiltration and inflammation. Male mice (8 weeks old) were made hypertensive by providing them with L-arginine methyl ester hydrochloride (L-NAME) (0.5 mg/mL) in the drinking water for 3 weeks and control mice received tap water. Testes of hypertensive mice had a significant increase in gene expression of the lymphatic vessel markers Lyve-1 (17.7 ± 2.1 fold; p<0.05), Podoplanin (6.7 ± 1.2 fold; p<0.05), and Prox-1 (68.1 ± 10.6 fold; p<0.05), the lymphangiogenic growth factors VEGF-C (5.7 ± 1.1 fold; p<0.05), VEGF-D (2.2 ± 0.7 fold; p<0.05), and VEGF-A (5.8 ± 1.1 fold; p<0.05) and their receptors VEGFR-2 (8.0 ± 2.0 fold; p<0.05) and VEGFR-3 (25.4 ± 3.5 fold; p<0.05). There was also a significant increase in the expression of the pro-inflammatory cytokines TNF-a (24.0 ± 6.8 fold; p<0.05), IFN-g (17.5 ± 3.0 fold; p<0.05), IL-1b (4.2 ± 1.2 fold; p<0.05), IL-6 (24.8 ± 13.0 fold; p<0.05), and IL-17 (4.4 ± 0.4 fold; p<0.05). There were also increases in the lymphatic endothelial cell-derived immune cell trafficking chemokines CCL21 (7.8 ± 1.7 fold; p<0.05) and CCL19 (9.0 ± 4.1 fold; p<0.05) and their receptor CCR7 (9.6 ± 3.2 fold; p<0.05), as well as the cell adhesion molecule ICAM (6.2 ± 1.0 fold; p<0.05) in testes of hypertensive mice. Flow cytometry analysis revealed an increased accumulation of F4/80+ macrophages in the testes from hypertensive mice. Together, these data demonstrate that HTN induces inflammation-associated lymphangiogenesis in testes, in association with immune cell infiltration. It is possible that increasing testicular lymphatics may reduce inflammation and improve reproductive function in hypertensive men.

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WISP1 modulates immune cell infiltration upon drug-induced liver injury (DILI)

Zeitschrift für Gastroenterologie ◽

10.1055/s-0035-1567970 ◽

2015 ◽

Vol 53 (12) ◽

Author(s):

AB Widera ◽

L Pütter ◽

S Leserer ◽

G Campos ◽

K Rochlitz ◽

...

Keyword(s):

Liver Injury ◽

Immune Cell ◽

Cell Infiltration ◽

Immune Cell Infiltration ◽

Drug Induced ◽

Drug Induced Liver Injury

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Faculty Opinions recommendation of Human breast cancer invasion and aggression correlates with ECM stiffening and immune cell infiltration.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725485692.793517744 ◽

2016 ◽

Author(s):

Paul Timpson ◽

Claire Vennin

Keyword(s):

Breast Cancer ◽

Human Breast Cancer ◽

Immune Cell ◽

Cancer Invasion ◽

Cell Infiltration ◽

Immune Cell Infiltration ◽

Human Breast ◽

Breast Cancer Invasion

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Identification of Potential Therapeutic Targets and Immune Cell Infiltration Characteristics in Osteosarcoma Using Bioinformatics Strategy

Frontiers in Oncology ◽

10.3389/fonc.2020.01628 ◽

2020 ◽

Vol 10 ◽

Author(s):

Jianfang Niu ◽

Taiqiang Yan ◽

Wei Guo ◽

Wei Wang ◽

Zhiqing Zhao ◽

...

Keyword(s):

Immune Cell ◽

Therapeutic Targets ◽

Cell Infiltration ◽

Immune Cell Infiltration

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SFTPA1 is a potential prognostic biomarker correlated with immune cell infiltration and response to immunotherapy in lung adenocarcinoma

Cancer Immunology Immunotherapy ◽

10.1007/s00262-021-02995-4 ◽

2021 ◽

Author(s):

Lu Yuan ◽

Xixi Wu ◽

Longshan Zhang ◽

Mi Yang ◽

Xiaoqing Wang ◽

...

Keyword(s):

Lung Cancer ◽

T Cells ◽

Lung Adenocarcinoma ◽

Expression Profile ◽

Immune Cell ◽

Cell Infiltration ◽

Immune Cell Infiltration ◽

Regulatory Pathways ◽

Chronic Lung Diseases ◽

Potential Biomarker

AbstractPulmonary surfactant protein A1 (SFTPA1) is a member of the C-type lectin subfamily that plays a critical role in maintaining lung tissue homeostasis and the innate immune response. SFTPA1 disruption can cause several acute or chronic lung diseases, including lung cancer. However, little research has been performed to associate SFTPA1 with immune cell infiltration and the response to immunotherapy in lung cancer. The findings of our study describe the SFTPA1 expression profile in multiple databases and was validated in BALB/c mice, human tumor tissues, and paired normal tissues using an immunohistochemistry assay. High SFTPA1 mRNA expression was associated with a favorable prognosis through a survival analysis in lung adenocarcinoma (LUAD) samples from TCGA. Further GeneOntology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses showed that SFTPA1 was involved in the toll-like receptor signaling pathway. An immune infiltration analysis clarified that high SFTPA1 expression was associated with an increased number of M1 macrophages, CD8+ T cells, memory activated CD4+ T cells, regulatory T cells, as well as a reduced number of M2 macrophages. Our clinical data suggest that SFTPA1 may serve as a biomarker for predicting a favorable response to immunotherapy for patients with LUAD. Collectively, our study extends the expression profile and potential regulatory pathways of SFTPA1 and may provide a potential biomarker for establishing novel preventive and therapeutic strategies for lung adenocarcinoma.

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Enhanced CD4+ and CD8+ T cell infiltrate within convex hull defined pancreatic islet borders as autoimmune diabetes progresses

Scientific Reports ◽

10.1038/s41598-021-96327-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Alexander J. Dwyer ◽

Jacob M. Ritz ◽

Jason S. Mitchell ◽

Tijana Martinov ◽

Mohannad Alkhatib ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Convex Hull ◽

Pancreatic Islets ◽

Immune Cell ◽

Nod Mice ◽

Cell Infiltration ◽

Immune Cell Infiltration ◽

Analytical Strategy ◽

Islet Mass

AbstractThe notion that T cell insulitis increases as type 1 diabetes (T1D) develops is unsurprising, however, the quantitative analysis of CD4+ and CD8+ T cells within the islet mass is complex and limited with standard approaches. Optical microscopy is an important and widely used method to evaluate immune cell infiltration into pancreatic islets of Langerhans for the study of disease progression or therapeutic efficacy in murine T1D. However, the accuracy of this approach is often limited by subjective and potentially biased qualitative assessment of immune cell subsets. In addition, attempts at quantitative measurements require significant time for manual analysis and often involve sophisticated and expensive imaging software. In this study, we developed and illustrate here a streamlined analytical strategy for the rapid, automated and unbiased investigation of islet area and immune cell infiltration within (insulitis) and around (peri-insulitis) pancreatic islets. To this end, we demonstrate swift and accurate detection of islet borders by modeling cross-sectional islet areas with convex polygons (convex hulls) surrounding islet-associated insulin-producing β cell and glucagon-producing α cell fluorescent signals. To accomplish this, we used a macro produced with the freeware software ImageJ equipped with the Fiji Is Just ImageJ (FIJI) image processing package. Our image analysis procedure allows for direct quantification and statistical determination of islet area and infiltration in a reproducible manner, with location-specific data that more accurately reflect islet areas as insulitis proceeds throughout T1D. Using this approach, we quantified the islet area infiltrated with CD4+ and CD8+ T cells allowing statistical comparison between different age groups of non-obese diabetic (NOD) mice progressing towards T1D. We found significantly more CD4+ and CD8+ T cells infiltrating the convex hull-defined islet mass of 13-week-old non-diabetic and 17-week-old diabetic NOD mice compared to 4-week-old NOD mice. We also determined a significant and measurable loss of islet mass in mice that developed T1D. This approach will be helpful for the location-dependent quantitative calculation of islet mass and cellular infiltration during T1D pathogenesis and can be combined with other markers of inflammation or activation in future studies.

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