scholarly journals Multi-tier mechanics control stromal adaptations in swelling lymph nodes

2021 ◽  
Author(s):  
Frank P. Assen ◽  
Miroslav Hons ◽  
Robert Hauschild ◽  
Shayan Shamipour ◽  
Jun Abe ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Immune Cell ◽  
Fold Increase ◽  
Cell Interaction ◽  
Solid Organ ◽  
Structural Elements ◽  
Pressure Force ◽  
Cell Matrix ◽  
Reticular Cells ◽  
Typical Configuration

Lymph nodes (LNs) comprise two main structural elements: Fibroblastic reticular cells (FRCs) that form dedicated niches for immune cell interaction and capsular fibroblasts that build a shell around the organ. While LNs are fairly stable in size during homeostatic conditions, immunological challenge causes more than 10-fold increase in size within only a few days. How a solid organ can accommodate such extreme volumetric changes is poorly understood. Here, we characterize the biomechanics of LN swelling on the cellular and organ scale. We identify lymphocyte trapping by influx and proliferation as drivers of an outward pressure force, causing FRCs and their associated conduits to stretch. After an initial phase of relaxation, FRCs sense the resulting strain via cell matrix adhesions, which coordinates local growth and remodeling of the stromal network. While the expanded FRC network adopts its typical configuration, a massive fibrotic reaction of the organ capsule sets in and counters further organ expansion. Thus, different fibroblast populations mechanically control LN swelling in a multi-tier fashion.

Endothelial Cell-Immune Cell Interaction in IBD

2016 ◽  
Vol 34 (1-2) ◽  
pp. 43-50 ◽  
Author(s):  
Silvio Danese ◽  
Claudio Fiocchi
Keyword(s):  
Endothelial Cells ◽  
Immune Cells ◽  
Bowel Wall ◽  
Regulatory Mechanism ◽  
Immune Cell ◽  
Cell Interaction ◽  
Mesenteric Lymph Nodes ◽  
Mesenteric Lymph ◽  
Inflammatory Bowel ◽  
Lymphatic Fluid

The proper delivery of immune cells throughout the host's various tissues and organs is essential to health, and abnormalities in the type and quantity of leukocyte distribution is usually associated with disease. Because of its size and presence of a very large amount of immunocytes in the mucosa and mesenteric lymph nodes, the gut is the recipient of a constant influx of leukocytes, a process tightly regulated by multiple factors. These include cell adhesion molecules on the leukocytes and their counter-receptors on the microvascular endothelial cells in the bowel wall, a number of chemokines and cytokines that help attracting immune cells, platelets, bacterial products, danger signals, the size of the vascular and lymphatic beds and the process of leukocyte exit and circulation in the blood and lymphatic fluid. The disruption of any of the above regulatory mechanism can lead to inflammation, as is the case for inflammatory bowel disease. Learning how leukocyte and endothelial cells mutually function in health and what goes wrong in inflammation offers the opportunity to intervene therapeutically and re-establish the normal crosstalk between leukocytes and endothelial cells.

HEVs, lymphatics and homeostatic immune cell trafficking in lymph nodes

2012 ◽  
Vol 12 (11) ◽  
pp. 762-773 ◽  
Author(s):  
Jean-Philippe Girard ◽  
Christine Moussion ◽  
Reinhold Förster
Keyword(s):  
Lymph Nodes ◽  
Immune Cell ◽  
Cell Trafficking ◽  
Immune Cell Trafficking

scholarly journals Immune Cell Profiles and Cytokine Levels of Patients with Interstitial Cystitis/Bladder Pain Syndrome

2020 ◽  
Author(s):  
Robert M. Moldwin ◽  
Vishaan Nursey ◽  
Oksana Yaskiv ◽  
Siddhartha Dalvi ◽  
Michael Funaro ◽  
...  
Keyword(s):  
Interstitial Cystitis ◽  
Plasma Cells ◽  
Immune Cell ◽  
Pain Syndrome ◽  
Fold Increase ◽  
Bladder Pain Syndrome ◽  
Bladder Tissue ◽  
Bladder Pain ◽  
Tnf Α ◽  
Significant Difference

AbstractAimsTo quantify the number of immune cells in the bladder urothelium and concentrations of urinary cytokines in patients with Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS). To identify differences in these measures in IC/BPS patients with Hunner’s lesions (IC/BPS-HL) and without Hunner’s lesions (IC/BPS-NHL).MethodsBladder tissue biopsies were obtained from 48 patients with IC/BPS-HL and unaffected controls (UC) and stained with antibodies for various immune cell markers such as CD138, CD20 and CD56. Levels of cytokines (Interferon (IFN)-γ, Interleukin (IL)-1β, IL-2, IL- 4, IL-6, IL-8, IL12P70, IL-13, and TNF-α) were measured from normalized urine obtained from 18 IC/BPS-HL, 18 IC/BPS-NHL, and 4 UC.ResultsNumbers of CD138+ plasma cells, CD20+ B cells, and CD3+ T cells were significantly increased (50 fold, 30 fold, and an almost 3 fold increase, respectively; p-values: 1.34E-06, 3.26E-04, and 2.52E-6) in the bladders of IC/BPS-HL patients compared to UC. Patients with IC/BPS-HL had significantly elevated urinary levels of IL-6 (p=0.0028) and TNF-α (p=0.009) compared to patients with IC/BPS-NHL and UC. In contrast, IL-12p70 levels were significantly higher in the patients with IC/BPS-NHL than in HL patients (p=0.033). No significant difference in IL-12p70 levels were observed between IC/BPS-HL and UC.ConclusionDifferent cytokines were elevated in the urine of IC/BPS patients with and without HL, suggesting differences in underlying disease processes. Elevated levels of CD138+, CD20+, and CD3+ cells in HL indicate B and T-cell involvement in lesion formation. Determining which cytokines and immunological pathways are present in IC/BPS-HL could elucidate the disease mechanism.

scholarly journals Advanced Genomics-Based Approaches for Defining Allograft Rejection With Single Cell Resolution

2021 ◽  
Vol 12 ◽  
Author(s):  
Tiffany Shi ◽  
Krishna Roskin ◽  
Brian M. Baker ◽  
E. Steve Woodle ◽  
David Hildeman
Keyword(s):  
Single Cell ◽  
Allograft Rejection ◽  
Immune Cell ◽  
Transplant Rejection ◽  
Solid Organ Transplantation ◽  
Genomic Analysis ◽  
Solid Organ ◽  
Single Cell Level ◽  
Cell Level ◽  
Network Analyses

Solid organ transplant recipients require long-term immunosuppression for prevention of rejection. Calcineurin inhibitor (CNI)-based immunosuppressive regimens have remained the primary means for immunosuppression for four decades now, yet little is known about their effects on graft resident and infiltrating immune cell populations. Similarly, the understanding of rejection biology under specific types of immunosuppression remains to be defined. Furthermore, development of innovative, rationally designed targeted therapeutics for mitigating or preventing rejection requires a fundamental understanding of the immunobiology that underlies the rejection process. The established use of microarray technologies in transplantation has provided great insight into gene transcripts associated with allograft rejection but does not characterize rejection on a single cell level. Therefore, the development of novel genomics tools, such as single cell sequencing techniques, combined with powerful bioinformatics approaches, has enabled characterization of immune processes at the single cell level. This can provide profound insights into the rejection process, including identification of resident and infiltrating cell transcriptomes, cell-cell interactions, and T cell receptor α/β repertoires. In this review, we discuss genomic analysis techniques, including microarray, bulk RNAseq (bulkSeq), single-cell RNAseq (scRNAseq), and spatial transcriptomic (ST) techniques, including considerations of their benefits and limitations. Further, other techniques, such as chromatin analysis via assay for transposase-accessible chromatin sequencing (ATACseq), bioinformatic regulatory network analyses, and protein-based approaches are also examined. Application of these tools will play a crucial role in redefining transplant rejection with single cell resolution and likely aid in the development of future immunomodulatory therapies in solid organ transplantation.

EPCO-32. IDENTIFICATION OF PROGNOSTIC CHORDOMA SUBGROUPS USING DNA METHYLATION SIGNATURES IN TISSUE AND PLASMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi9-vi9
Author(s):  
Jeffrey Zuccato ◽  
Vikas Patil ◽  
Sheila Mansouri ◽  
Jeffrey Liu ◽  
Farshad Nassiri ◽  
...  
Keyword(s):  
Dna Methylation ◽  
High Throughput Sequencing ◽  
Linear Models ◽  
Immune Cell ◽  
Spinal Metastases ◽  
Treatment Decision ◽  
Cell Interaction ◽  
Patient Treatment ◽  
Consensus Clustering ◽  
Treatment Decision Making

Abstract BACKGROUND Chordomas are malignant bone cancers arising from the skull-base and spine that are rare but cause devastating central nervous system morbidities. Survival is highly variable despite surgery and radiotherapy as 10% live under 1 year and 30-35% survive over 20 years. There are currently no reliable prognostic factors and this limits our ability to tailor patient treatment to their risk. Accordingly, this work identifies epigenetic prognostic chordoma subgroups that are detectable non-invasively through plasma methylomes to guide treatment. METHODS A total of 68 chordoma surgical specimens resected between 1996-2018 across three international centres underwent DNA methylation profiling. Cell-free methylated tumor DNA immunoprecipitation and high-throughput sequencing was performed on available matched plasma samples. RESULTS Two stable tumor clusters were identified through consensus clustering of tissue methylation data. Clusters had statistically significantly different disease-specific survivals (log-rank p=0.0062) independent of clinical factors in a multivariable Cox analysis (HR=16.5, 95%CI: 2.8-96, p=0.0018). The poorer-performing “Immune-infiltrated” cluster had genes hypomethylated at promoters, typically resulting in transcription, within immune-related pathways and higher immune cell abundance within tumors. The better-performing “Cellular” cluster showed higher tumor cellularity plus cell-to-cell interaction and extracellular matrix pathway hypomethylation. Fifty chordoma-versus-other binomial generalized linear models built using plasma methylome data distinguished chordomas from meningiomas and spinal metastases, as representative clinical differential diagnoses, in random left-out 20% testing sets (mean AUROC=0.84, 95%CI: 0.52-1.00). Plasma-based methylation signatures were highly correlated with tissue-based signals within both poor-performing (median r=0.69, 95%CI: 0.66-0.72) and better-performing cluster tumors (median r=0.67, 95%CI: 0.62-0.72). CONCLUSIONS The first identification of two distinct prognostic epigenetic chordoma subgroups is shown here with “Immune-infiltrated” tumors having a poorer prognosis than “Cellular” tumors. Plasma methylomes can be utilized for non-invasive chordoma diagnosis and subtyping. This work may transform chordoma treatment decision-making by guiding surgical planning in advance to match resection aggressiveness with patient prognosis.

Abstract 16504: Low Disturbed Flow Induces Dynamic Immune Compartment Alterations in Atherogenesis as Revealed by Single Cell Rna-seq

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Lili Qu ◽  
Chuan Li ◽  
Alyssa Matz ◽  
Annabelle Rodriguez-Oquendo ◽  
Anthony Vella ◽  
...  
Keyword(s):  
Immune Cell ◽  
Paired Comparison ◽  
Cell Types ◽  
Cell Interaction ◽  
Artery Ligation ◽  
Human Artery ◽  
Disturbed Flow ◽  
Signature Genes ◽  
Sheer Stress ◽  
The Impact

Low disturbed blood flow (LDF) is a critical contributing factor to atherogenesis but its direct impact on the immune compartment was not well-depict. To fill this knowledge gap, we adopted scRNA-seq to capture sheer-stress induced immune responses during atherogenesis. A partial carotid artery ligation (PCAL) model was selected for its paired comparison of carotid arteries with normal flow (NF) or LDF. Indeed, we observed drastic changes in both endothelial and immune compartment. Macrophages were the most significantly increased population induced by LDF (from 4% to 12% of CD45+ cells) with two well-separated subsets (Mac-c8, Mac-c9). MacSpectrum analyses revealed that Mac-c8 displayed higher inflammatory states than the lipid-laden Mac-c9. Interestingly, three T subtypes displayed unique flow-induced enrichment patterns that were selectively enriched in LDF but not in the NF condition. Furthermore, we created an original algorithms to evaluate the impact of sheer-stress on membrane protein-mediated cell-cell interaction among all cell types in the atheroma. Several pairs of molecular interactions were identified, including multiple APP-ligands interaction pairs and those in BAG2 Signaling. Moreover, signature genes identified in these LDF-induced T cells displayed high correlation to the plaque severity in human artery-aorta samples. Collectively, our study provided a high-resolution and focused analyses of sheer-stress induced immune cell action during atherogenesis. This is also the first identification of unique T subsets, to our knowledge, that are enriched in arterial wall exposed to low and disturbed flow. Further characterization of these cells will provide valuable information to understand and therapeutically treat atherogenesis.

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