scholarly journals The Polygenic Map of Keloid Fibroblasts Reveals Fibrosis-Associated Gene Alterations in Inflammation and Immune Responses

2022 ◽  
Vol 12 ◽  
Author(s):  
Yang Li ◽  
Min Li ◽  
Caijie Qu ◽  
Yongxi Li ◽  
Zhanli Tang ◽  
...  
Keyword(s):  
T Cells ◽  
Signaling Pathways ◽  
Protein Interactions ◽  
Immune Cell ◽  
Normal Skin ◽  
Cell Activity ◽  
Scar Tissue ◽  
Gene Expression Omnibus ◽  
Genomic Expression ◽  
Keloid Formation

Due to many inconsistencies in differentially expressed genes (DEGs) related to genomic expression changes during keloid formation and a lack of satisfactory prevention and treatment methods for this disease, the critical biomarkers related to inflammation and the immune response affecting keloid formation should be systematically clarified. Normal skin/keloid scar tissue-derived fibroblast genome expression data sets were obtained from the Gene Expression Omnibus (GEO) and ArrayExpress databases. Hub genes have a high degree of connectivity and gene function aggregation in the integration network. The hub DEGs were screened by gene-related protein–protein interactions (PPIs), and their biological processes and signaling pathways were annotated to identify critical biomarkers. Finally, eighty-one hub DEGs were selected for further analysis, and some noteworthy signaling pathways and genes were found to be closely related to keloid fibrosis. For example, IL17RA is involved in IL-17 signal transduction, TIMP2 and MMP14 activate extracellular matrix metalloproteinases, and TNC, ITGB2, and ITGA4 interact with cell surface integrins. Furthermore, changes in local immune cell activity in keloid tissue were detected by DEG expression, immune cell infiltration, and mass CyTOF analyses. The results showed that CD4+ T cells, CD8+ T cells and NK cells were abnormal in keloid tissue compared with normal skin tissue. These findings not only support the key roles of fibrosis-related pathways, immune cells and critical genes in the pathogenesis of keloids but also expand our understanding of targets that may be useful for the treatment of fibrotic diseases.

scholarly journals Integrative Analysis of Minichromosome Maintenance Proteins and Their Prognostic Significance in Melanoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Wei Han ◽  
Yi-Zhu Wu ◽  
Xiao-Yu Zhao ◽  
Zhen-Hua Gong ◽  
Guo-Liang Shen
Keyword(s):  
T Cells ◽  
Cell Cycle Progression ◽  
Immune Cell ◽  
Normal Skin ◽  
Expression Patterns ◽  
Prognostic Significance ◽  
Mrna Levels ◽  
Minichromosome Maintenance ◽  
Prognostic Accuracy ◽  
Mtorc1 Signaling

BackgroundMinichromosome maintenance (MCM) is known for participating in cell cycle progression, as well as DNA replication. While the diverse expression patterns and prognostic values of MCMs in melanoma still remained unclear.MethodsIn the present study, the transcriptional and clinical profiles of MCMs were explored in patients with melanoma from multiple databases, including GEO, TCGA, ONCOMINE, GEPIA, UALCAN, cBioPortal, and TIMER databases.ResultsWe found that the elevated expressions of MCM2–6 and MCM10 were significantly expressed in melanoma compared to normal skin. High mRNA levels of MCM4, MCM5, and MCM10 were closely related to worse prognosis in patients with melanoma. GSEA showed hallmark pathways were most involved in mTORC1 signaling, G2M checkpoint, E2F targets, and mitotic spindle. Furthermore, we found potential correlations between the MCM expression and the immune cell infiltration, including B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells.ConclusionUpregulated MCM gene expression in melanoma probably played a crucial part in the development and progression of melanoma. The upregulated MCM4/5/10 expressions could be used as potential prognostic markers to improve the poor outcome and prognostic accuracy in patients with melanoma. Our study might shed light on the selection of prognostic biomarkers as well as the underlying molecular pathogenesis of melanoma.

scholarly journals DNA-scaffolded biomaterials enable modular and tunable control of cell-based cancer immunotherapies

2019 ◽  
Author(s):  
Xiao Huang ◽  
Jasper Z. Williams ◽  
Ryan Chang ◽  
Zhongbo Li ◽  
Eric Gai ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Cell ◽  
Ex Vivo ◽  
Cell Activity ◽  
Engineered T Cells ◽  
Advanced Biomaterials ◽  
Cancer Immunotherapies ◽  
Biodegradable Particles ◽  
The Impact

Advanced biomaterials provide versatile ways to spatially and temporally control immune cell activity, potentially enhancing their therapeutic potency and safety. Precise cell modulation demands multi-modal display of functional proteins with controlled densities on biomaterials. Here, we develop an artificial immune cell engager (AICE) platform – biodegradable particles onto which multiple proteins are densely loaded with ratiometric control via short nucleic acid tethers. We demonstrate the impact of AICE with varying ratios of anti-CD3 and anti-CD28 antibodies onex vivoexpansion of human primary T cells. We also show that AICE can be used to control the activity of engineered T cellsin vivo. AICE injected intratumorally can provide a local priming signal for systemically administered AND-gate chimeric antigen receptor T cells, driving local tumor clearance while sparing uninjected tumors that model potentially cross-reactive healthy tissues. This modularly functionalized biomaterial thus provides a flexible platform to achieve sophisticated control over cell-based immunotherapies.

scholarly journals Schwann cells contribute to keloid formation

2021 ◽  
Author(s):  
Martin Direder ◽  
Tamara Weiss ◽  
Dragan Copic ◽  
Vera Vorstandlechner ◽  
Maria Laggner ◽  
...  
Keyword(s):  
Schwann Cells ◽  
Normal Skin ◽  
Scar Tissue ◽  
Functional Impairments ◽  
Novel Treatment ◽  
M2 Polarization ◽  
Keloid Formation ◽  
Hypertrophic Scar Tissue ◽  
Schwann Cell Differentiation ◽  
Abundant Population

Keloids are disfiguring, hypertrophic scars with yet poorly understood pathomechanisms, which could lead to severe functional impairments. Here we analyzed the characteristics of keloidal cells by single cell sequencing and discovered the presence of an abundant population of Schwann cells that persisted in the hypertrophic scar tissue after wound healing. In contrast to normal skin, keloidal Schwann cells possess a repair-like phenotype and high cellular plasticity. Our data support the hypothesis that keloidal Schwann cells contribute to the formation of the extracellular matrix and are able to affect M2 polarization of macrophages. Indeed, we show that macrophages in keloids predominantly display a M2 polarization and produce factors that inhibit Schwann cell differentiation. Our data suggest a contribution of this cross-talk to the continuous expansion of keloids, and that targeting Schwann cells might represent an interesting novel treatment option for keloids.

scholarly journals Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses

2021 ◽  
Author(s):  
Rouven Schulz ◽  
Medina Korkut-Demirbaş ◽  
Gloria Colombo ◽  
Sandra Siegert
Keyword(s):  
Signaling Pathways ◽  
Protein Interactions ◽  
Immune Cell ◽  
Signal Transmission ◽  
The Body ◽  
Cell Type ◽  
Protein Protein Interactions ◽  
Β2 Adrenergic Receptor ◽  
Neuronal Signal ◽  
And Function

G protein-coupled receptors (GPCRs) regulate multiple processes ranging from cell growth and immune responses to neuronal signal transmission. However, ligands for many GPCRs remain unknown, suffer from off-target effects or have poor bioavailability. Additional challenges exist to dissect cell type-specific responses when the same GPCR is expressed on different cells within the body. Here, we overcome these limitations by engineering DREADD-based GPCR chimeras that selectively bind their agonist clozapine-N-oxide (CNO) and mimic a GPCR-of-interest. We show that the chimeric DREADD-β2-adrenergic receptor (β2AR/ADRB2) triggers comparable responses to levalbuterol on second messenger and kinase activity, post-translational modifications, and protein-protein interactions. Moreover, we successfully recapitulate β2AR-mediated filopodia formation in microglia, a β2AR-expressing immune cell that can drive inflammation in the nervous system. To further dissect microglial inflammation, we compared DREADD-β2AR with two additionally designed DREADD-based chimeras mimicking GPR65 and GPR109A/HCAR2, both enriched in microglia. DREADD-β2AR and DREADD-GPR65 modulate the inflammatory response with a similar profile as endogenously expressed β2AR, while DREADD-GPR109A had no impact. Our DREADD-based approach allows investigation of cell type-dependent signaling pathways and function without known endogenous ligands.

6,7,4′-Trihydroxyflavanone Prevents Methamphetamine-Induced T Cell Deactivation by Protecting the Activated T Cells from Apoptosis

2021 ◽  
pp. 1-17
Author(s):  
Hyun-Su Lee ◽  
Gil-Saeng Jeong
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Immune Cell ◽  
Therapeutic Potential ◽  
Cell Activity ◽  
Activated T Cells ◽  
Study Results ◽  
Apoptotic Proteins ◽  
Pre Treatment

Methamphetamine (METH) is an extremely addictive drug that has raised serious public health concerns recently. METH addiction not only results in neuronal cytotoxicity, but it also affects immune cell activity, including T lymphocytes. 6,4,7[Formula: see text]-trihydroxyflavanone (THF), isolated from Dalbergia odorifera, has been studied for its antibacterial activity, but evidence for whether THF has an anti-cytotoxic and protective effect on T cell activation exposed to METH is lacking. In this study, results showed that treatment with THF was not cytotoxic to Jurkat T cells but dose-dependently mitigated the cytotoxicity induced by exposure to METH. The Western blot results demonstrating pre-treatment with THF maintained the expression of anti-apoptotic proteins and phosphorylation of PI3K/Akt/mTOR downregulated by treatment with METH. Furthermore, we found that decreased expression of IL-2 and CD69 by METH exposure was partially restored, and viability was significantly prevented by pre-treatment with THF in activated T cells. These findings were involved in re-elevated expression of anti-apoptotic proteins as well as recovered pathways including MAPK/PI3K/Akt/mTOR in activated T cells pre-exposed to METH. Our results suggest beneficial effects of THF against the cytotoxic and immune-modulating effect of METH on T cells and therapeutic potential of THF for patients with immunodeficiency caused by METH addiction.

scholarly journals Hypertrophic Scars and Keloids – Contemporary Concepts and Treatment Options

2014 ◽  
Vol 41 (1) ◽  
pp. 57-74 ◽  
Author(s):  
Y. P. Yordanov ◽  
A. Shef
Keyword(s):  
Wound Healing ◽  
Normal Skin ◽  
Treatment Options ◽  
Cell Activity ◽  
Scar Tissue ◽  
Medical Problem ◽  
Scar Formation ◽  
Hypertrophic Scars ◽  
Inflammatory Processes ◽  
Reparative Process

Summary Wound reparative process after surgery, burns, injuries, and inflammatory processes results in a spectrum of scar formation ranging from nearly scarless healing to excessive fibrosis or atrophy. Scarring is considered a major medical problem that leads to aesthetic and functional sequelae. Scar tissue is clinically distinguished from normal skin by an aberrant color, rough surface texture, increased thickness (hypertrophy), occurrence of contraction, and firmness. In the last decade, the concept of wound healing kinetics has been developed to describe the delicate balance of cell activity involved in scar formation and remodeling. Hypertrophic scars and keloids are formed as a result of the process of abnormal wound healing. Despite all that has been written on improving the appearance of these types of scars, there are no definitive management protocols. The aim of the present article is to make a brief review of the basic wound healing, while focusing on medicine’s latest understanding of the development and treatment of keloids and hypertrophic scars.

scholarly journals A dual immune signature of CD8+ T Cells and MMP9 improves the survival of hepatocellular carcinoma patients

2021 ◽  
Author(s):  
Huan Ding ◽  
Huan Hu ◽  
Feifei Tian ◽  
Huaping Liang
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Cd8 T Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Cox Regression ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
High Recurrence Rate ◽  
Immune Signature

The 5-year survival of hepatocellular carcinoma (HCC) is difficult due to the high recurrence rate and metastasis. Tumor infiltrating immune cells (TICs) and immune-related genes (IRGs) bring hope to improve survival and treatment of HCC patients. However, there are problems in predicting immune signatures and identifying novel therapeutic targets. In the study, the CIBERSORT algorithm was used to evaluate 22 immune cell infiltration patterns in gene expression omnibus (GEO) and the cancer genome atlas (TCGA) data. Eight immune cells were found to have significant infiltration differences between the tumor and normal groups. The CD8+ T Cells immune signature was constructed by least absolute shrinkage and selection operator (LASSO) algorithm. The high infiltration level of CD8+ T Cells could significantly improve survival of patients. The weighted gene co-expression network analysis (WGCNA) algorithm identified MMP9 was closely related to the overall survival of HCC patients. K-M survival and tROC analysis confirmed that MMP9 had an excellent prognostic prediction. Cox regression showed that a dual immune signature of CD8+ T Cells and MMP9 was independent survival factor in HCC. Therefore, a dual prognostic immune signature could improve the survival of patient and may provide a new strategy for the immunotherapy of HCC.

scholarly journals Regulatory T Cells Improved the Anti-cirrhosis Activity of Human Amniotic Mesenchymal Stem Cell in the Liver by Regulating the TGF-β-Indoleamine 2,3-Dioxygenase Signaling

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhenhua Deng ◽  
Jinren Zhou ◽  
Xiaoxin Mu ◽  
Jian Gu ◽  
Xiangyu Li ◽  
...  
Keyword(s):  
T Cells ◽  
Liver Fibrosis ◽  
Regulatory T Cells ◽  
Mesenchymal Stromal Cell ◽  
Immune Cell ◽  
Cell Activity ◽  
Indoleamine 2,3 Dioxygenase ◽  
Current Therapies ◽  
Hepatocyte Growth

Liver fibrosis is a progression stage of chronic liver disease, while current therapies cannot cure or attune cirrhosis effectively. Human amniotic mesenchymal stromal cell (hAMSC) presented immunoregulatory and tissue repairability of multiple illnesses. Regulatory T cells (Treg) had been proved to be functional in reducing immune cell activity. We showed that co-infusion of hAMSC and Treg prevented mild liver fibrosis comparing with hAMSC or Treg alone group. In vitro study indicated that the addition of Treg or the supernatant of Treg improved the hepatocyte growth factor (HGF) secreting and cell differentiation ability of hAMSC. Reduction of TGF-β significantly decreased the HGF secreting and differentiation of hAMSC. Multiple signal neutralizers were added to the culture to understand further the mechanism, which showed that 1-MT, the suppressor of Indoleamine 2,3-dioxygenase (IDO), was involved in the effect of TGF-β in regulating hAMSC. Depletion of TGF-β or IDO signaling successfully abolished the effect of Treg in improving hAMSC’s function both in vitro and vivo. Finally, our result indicated that Treg improved the function of hAMSC by regulating the TGF-β-IDO signaling and co-infusion of hAMSC and Treg provided a promising approach for treating liver cirrhosis.

scholarly journals Prognostic Biomarkers and Therapeutic Targets Identification Among CXC Chemokines in the Colon Adenocarcinoma Microenvironment

2022 ◽  
Author(s):  
Heng Wang ◽  
ChangQing Guo ◽  
Jun Luo ◽  
Quan Li ◽  
BuQing Fu ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Cell ◽  
Prognostic Significance ◽  
Cell Activity ◽  
Colon Adenocarcinoma ◽  
Prognostic Indicators ◽  
Chemokine Signaling ◽  
High Incidence ◽  
High Incidence Rate ◽  
Chemokine Signaling Pathway

Abstract Background: COAD is among the most prevalent malignancy, with a very high incidence rate. Crosstalk between cancer and interstitial cells significantly affects cancer development, modulated partly by chemokines production. When present in the tumor microenvironment, CXC chemokines have been shown to regulate tumor cell activity and influence immune cell transport, resulting in anti-tumor immune mechanisms and influencing the outcomes of the patient; nonetheless, the CXC chemokines expression levels in COAD, as well as their prognostic significance, have not yet been established.Methods: This study used UALCAN, GeneMANIA, STRING, TRRUST, cBioPortal, TIMER, and GEPIA,Results: The expression of CXC1/2/3/5/6/11/12/13/14/16/17 in COAD patients was shown to be significantly correlated with the pathological stage. A considerably improved prognosis was observed in patients with low transcriptional levels of CXCL9/10/11. Differentially expressed CXC chemokines exert roles that are predominantly correlated with the chemokine signaling pathway and interactions of cytokine–cytokine receptors. Our findings indicated that the transcriptional factors, including SP1, RELA, and NFKB1 are essential for the production of CXC chemokines. Furthermore, we discovered a substantial association between the CXC chemokines production and infiltration of 6 kinds of immune cells (CD8+ T cells, dendritic cells, B cells, CD4+ T cells, neutrophils, and macrophages,). Conclusions: These findings might be useful in identifying prognostic indicators and immunotherapeutic targets for colon cancer.

scholarly journals Complement Has Brains—Do Intracellular Complement and Immunometabolism Cooperate in Tissue Homeostasis and Behavior?

2021 ◽  
Vol 12 ◽  
Author(s):  
Natalia Kunz ◽  
Claudia Kemper
Keyword(s):  
T Cells ◽  
Immune Cells ◽  
Complement System ◽  
Immune Cell ◽  
Cell Activity ◽  
Metabolic Reprogramming ◽  
Normal Brain ◽  
Peripheral Tissues ◽  
Ifn Γ ◽  
The Brain

The classical liver-derived and serum-effective complement system is well appreciated as a key mediator of host protection via instruction of innate and adaptive immunity. However, recent studies have discovered an intracellularly active complement system, the complosome, which has emerged as a central regulator of the core metabolic pathways fueling human immune cell activity. Induction of expression of components of the complosome, particularly complement component C3, during transmigration from the circulation into peripheral tissues is a defining characteristic of monocytes and T cells in tissues. Intracellular complement activity is required to induce metabolic reprogramming of immune cells, including increased glycolytic flux and OXPHOS, which drive the production of the pro-inflammatory cytokine IFN-γ. Consequently, reduced complosome activity translates into defects in normal monocyte activation, faulty Th1 and cytotoxic T lymphocyte responses and loss of protective tissue immunity. Intriguingly, neurological research has identified an unexpected connection between the physiological presence of innate and adaptive immune cells and certain cytokines, including IFN-γ, in and around the brain and normal brain function. In this opinion piece, we will first review the current state of research regarding complement driven metabolic reprogramming in the context of immune cell tissue entry and residency. We will then discuss how published work on the role of IFN-γ and T cells in the brain support a hypothesis that an evolutionarily conserved cooperation between the complosome, cell metabolism and IFN-γ regulates organismal behavior, as well as immunity.

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