scholarly journals Locus-specific induction of gene expression from heterochromatin loci during cellular senescence

2020 ◽  
Author(s):  
Kosuke Tomimatsu ◽  
Dóra Bihary ◽  
Ioana Olan ◽  
Aled Parry ◽  
Stefan Schoenfelder ◽  
...  
Keyword(s):  
Cellular Senescence ◽  
Immune Cells ◽  
Nuclear Periphery ◽  
Open Chromatin ◽  
Facultative Heterochromatin ◽  
Specific Induction ◽  
Functional Relevance ◽  
Heterochromatic Genes ◽  
Chromatin Reorganization

Abstract Cellular senescence is a fate-determined state, accompanied by reorganization of heterochromatin. While lineage-appropriate genes can be temporarily repressed through facultative heterochromatin, stable silencing of lineage-inappropriate genes often involves the constitutive heterochromatic mark, histone H3K9me3. The fate of these heterochromatic genes during the chromatin reorganization accompanying senescence is unclear. Here we show a small number of lineage-inappropriate genes are derepressed in senescent cells from H3K9me3 regions that gain open chromatin marks. DNA FISH experiments reveal that these gene loci, which are tightly condensed at the nuclear periphery in proliferative cells, are physically decompacted during senescence. Among these gene loci, NLRP3 is predominantly expressed in immune cells, such as macrophages, where it resides within an open topologically associated domain (TAD). In contrast, NLRP3 is derepressed in senescent fibroblasts, potentially due to the local disruption of the H3K9me3-rich TAD that contains it. The role of NLRP3 has been implicated in the amplification of inflammatory cytokine signalling in senescence and aging, underscoring the functional relevance of gene induction from ‘permissive’ H3K9me3 regions in senescent cells.

The Role of Chromatin Reorganization in the Process of Cellular Senescence

2012 ◽  
Vol 13 (13) ◽  
pp. 1593-1602 ◽  
Author(s):  
Kaoru Tominaga ◽  
Olivia M. Pereira-Smith
Keyword(s):  
Cellular Senescence ◽  
Chromatin Reorganization

PD-L1 Inhibitors for the Treatment of Prostate Cancer

2020 ◽  
Vol 21 (15) ◽  
pp. 1558-1565
Author(s):  
Matteo Santoni ◽  
Francesco Massari ◽  
Liang Cheng ◽  
Alessia Cimadamore ◽  
Marina Scarpelli ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
T Lymphocytes ◽  
Chronic Inflammation ◽  
Immune Cells ◽  
Response To Therapy ◽  
Complex Series

The carcinogenesis of prostate cancer (PCa) results from a complex series of events. Chronic inflammation and infections are crucial in this context. Infiltrating M2 type macrophages, as well as neutrophils and T lymphocytes, contribute to PCa development, progression and response to therapy. The preliminary findings on the efficacy of immunotherapy in patients with PCa were not encouraging. However, a series of studies investigating anti-PD-L1 agents such as Atezolizumab, Avelumab and Durvalumab used alone or in combination with other immunotherapies, chemotherapy or locoregional approaches are in course in this tumor. In this review, we illustrate the role of immune cells and PD-L1 expression during PCa carcinogenesis and progression, with a focus on ongoing clinical trials on anti-PD-L1 agents in this context.

The Role of α7nAChR-Mediated Cholinergic Anti-inflammatory Pathway in Immune Cells

Inflammation ◽  
2021 ◽  
Author(s):  
Yi-jin Wu ◽  
Li Wang ◽  
Chao-fan Ji ◽  
Shao-fei Gu ◽  
Qin Yin ◽  
...  
Keyword(s):  
Immune Cells ◽  
Inflammatory Pathway ◽  
Anti Inflammatory

Prevention of Dextran Sulfate Sodium-induced Mouse Colitis by a Fungal Protein Ling Zhi-8 via Promoting the Barrier Function of Intestinal Epithelial Cells

2021 ◽  
Author(s):  
Yu-Huan Chen ◽  
Jenn-Yeu Shin ◽  
Hsiu-Mei Wei ◽  
Chi-Chen Lin ◽  
Linda Chia-Hui Yu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Immune Cells ◽  
Ganoderma Lucidum ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Fungal Protein ◽  
Fungal Immunomodulatory Protein

A fungal immunomodulatory protein Ling Zhi-8 (LZ-8) isolated from Ganoderma lucidum (GL) regulates immune cells and inhibits tumor growth; however, the role of LZ-8 in intestinal epithelial cells (IECs) is...

The Role of Cellular Senescence in Werner Syndrome: Toward Therapeutic Intervention in Human Premature Aging

2007 ◽  
Vol 1100 (1) ◽  
pp. 455-469 ◽  
Author(s):  
T. DAVIS ◽  
F. S. WYLLIE ◽  
M. J. ROKICKI ◽  
M. C. BAGLEY ◽  
D. KIPLING
Keyword(s):  
Cellular Senescence ◽  
Therapeutic Intervention ◽  
Werner Syndrome ◽  
Premature Aging

scholarly journals Microfluidic tumor-on-a-chip model to evaluate the role of tumor environmental stress on NK cell exhaustion

2021 ◽  
Vol 7 (8) ◽  
pp. eabc2331 ◽  
Author(s):  
Jose M. Ayuso ◽  
Shujah Rehman ◽  
Maria Virumbrales-Munoz ◽  
Patrick H. McMinn ◽  
Peter Geiger ◽  
...  
Keyword(s):  
Nk Cells ◽  
Immune Cells ◽  
Molecular Mechanisms ◽  
Nk Cell ◽  
Checkpoint Inhibitors ◽  
Waste Product ◽  
Extended Period ◽  
Cell Exhaustion

Solid tumors generate a suppressive environment that imposes an overwhelming burden on the immune system. Nutrient depletion, waste product accumulation, hypoxia, and pH acidification severely compromise the capacity of effector immune cells such as T and natural killer (NK) cells to destroy cancer cells. However, the specific molecular mechanisms driving immune suppression, as well as the capacity of immune cells to adapt to the suppressive environment, are not completely understood. Thus, here, we used an in vitro microfluidic tumor-on-a-chip platform to evaluate how NK cells respond to the tumor-induced suppressive environment. The results demonstrated that the suppressive environment created by the tumor gradually eroded NK cell cytotoxic capacity, leading to compromised NK cell surveillance and tumor tolerance. Further, NK cell exhaustion persisted for an extended period of time after removing NK cells from the microfluidic platform. Last, the addition of checkpoint inhibitors and immunomodulatory agents alleviated NK cell exhaustion.

scholarly journals RhoA- and Actin-Dependent Functions of Macrophages from the Rodent Cardiac Transplantation Model Perspective -Timing Is the Essence

Biology ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 70
Author(s):  
Malgorzata Kloc ◽  
Ahmed Uosef ◽  
Martha Villagran ◽  
Robert Zdanowski ◽  
Jacek Z. Kubiak ◽  
...  
Keyword(s):  
Immune Response ◽  
Circadian Rhythm ◽  
Immune Cells ◽  
Chronic Rejection ◽  
Cardiac Transplantation ◽  
Small Gtpase ◽  
Eukaryotic Cells ◽  
Transplantation Model

The small GTPase RhoA, and its down-stream effector ROCK kinase, and the interacting Rac1 and mTORC2 pathways, are the principal regulators of the actin cytoskeleton and actin-related functions in all eukaryotic cells, including the immune cells. As such, they also regulate the phenotypes and functions of macrophages in the immune response and beyond. Here, we review the results of our and other’s studies on the role of the actin and RhoA pathway in shaping the macrophage functions in general and macrophage immune response during the development of chronic (long term) rejection of allografts in the rodent cardiac transplantation model. We focus on the importance of timing of the macrophage functions in chronic rejection and how the circadian rhythm may affect the anti-chronic rejection therapies.

scholarly journals Overexpressed pseudogene MT1L associated with tumor immune infiltrates and indicates a worse prognosis in BLCA

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yanpeng Ding ◽  
Nuomin Liu ◽  
Mengge Chen ◽  
Yulian Xu ◽  
Sha Fang ◽  
...  
Keyword(s):  
Immune Cells ◽  
Biological Function ◽  
Prognostic Biomarker ◽  
Poor Survival ◽  
Common Cancer ◽  
Kaplan Meier ◽  
Cox Analysis ◽  
Kaplan Meier Plotter ◽  
Worse Prognosis

Abstract Background BLCA is a common cancer worldwide, and it is both aggressive and fatal. Immunotherapy (ICT) has achieved an excellent curative effect in BLCA; however, only some BLCA patients can benefit from ICT. MT1L is a pseudogene, and a previous study suggested that MT1L can be used as an indicator of prognosis in colorectal cancer. However, the role of MT1L in BLCA has not yet been determined. Methods Data were collected from TCGA, and logistic regression, Kaplan-Meier plotter, and multivariate Cox analysis were performed to demonstrate the correlation between the pseudogene MT1L and the prognosis of BLCA. To identify the association of MT1L with tumor-infiltrating immune cells, TIMER and TISIDB were utilized. Additionally, GSEA was performed to elucidate the potential biological function. Results The expression of MT1L was decreased in BLCA. Additionally, MT1L was positively correlated with immune cells, such as Tregs (ρ = 0.708) and MDSCs (ρ = 0.664). We also confirmed that MT1L is related to typical markers of immune cells, such as PD-1 and CTLA-4. In addition, a high MT1L expression level was associated with the advanced T and N and high grade in BLCA. Increased expression of MT1L was significantly associated with shorter OS times of BLCA patients (p < 0.05). Multivariate Cox analysis revealed that MT1L expression could be an independent prognostic factor in BLCA. Conclusion Collectively, our findings demonstrated that the pseudogene MT1L regulates the immune microenvironment, correlates with poor survival, and is an independent prognostic biomarker in BLCA.

Pathological Alternations of Mediastinal Fat-Associated Lymphoid Cluster and Lung in a Streptozotocin-Induced Diabetic Mouse Model

2020 ◽  
pp. 1-14
Author(s):  
Yaser H.A. Elewa ◽  
Osamu Ichii ◽  
Teppei Nakamura ◽  
Yasuhiro Kon
Keyword(s):  
Endothelial Cells ◽  
Lung Injury ◽  
Mouse Model ◽  
Immune Cells ◽  
Inflammatory Markers ◽  
Inflammatory Marker ◽  
Diabetic Mouse ◽  
Control Group ◽  
Injury Progression

Diabetes is a devastating global health problem and is considered a predisposing factor for lung injury progression. Furthermore, previous reports of the authors revealed the role of mediastinal fat-associated lymphoid clusters (MFALCs) in advancing respiratory diseases. However, no reports concerning the role of MFALCs on the development of lung injury in diabetes have been published. Therefore, this study aimed to examine the correlations between diabetes and the development of MFALCs and the progression of lung injury in a streptozotocin-induced diabetic mouse model. Furthermore, immunohistochemical analysis for immune cells (CD3+ T-lymphocytes, B220+ B-lymphocytes, Iba1+ macrophages, and Gr1+ granulocytes), vessels markers (CD31+ endothelial cells and LYVE-1+ lymphatic vessels “LVs”), and inflammatory markers (TNF-α and IL-5) was performed. In comparison to the control group, the diabetic group showed lung injury development with a significant increase in MFALC size, immune cells, LVs, and inflammatory marker, and a considerable decrease of CD31+ endothelial cells in both lung and MFALCs was observed. Furthermore, the blood glucose level showed significant positive correlations with MFALCs size, lung injury, immune cells, inflammatory markers, and LYVE-1+ LVs in lungs and MFALCs. Thus, we suggest that the development of MFALCs and LVs could contribute to lung injury progression in diabetic conditions.

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