scholarly journals Pathological alteration and therapeutic implications of sepsis-induced immune cell apoptosis

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Chao Cao ◽  
Muming Yu ◽  
Yanfen Chai
Keyword(s):  
Inflammatory Response ◽  
Immune Cells ◽  
Cell Apoptosis ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Specific Treatment ◽  
Treatment Modalities ◽  
Initial State ◽  
Adaptive Immune Cells ◽  
Secondary Infections

Abstract Sepsis is a life-threatening organ dysfunction syndrome caused by dysregulated host response to infection that leads to uncontrolled inflammatory response followed by immunosuppression. However, despite the high mortality rate, no specific treatment modality or drugs with high efficacy is available for sepsis to date. Although improved treatment strategies have increased the survival rate during the initial state of excessive inflammatory response, recent trends in sepsis show that mortality occurs at a period of continuous immunosuppressive state in which patients succumb to secondary infections within a few weeks or months due to post-sepsis “immune paralysis.” Immune cell alteration induced by uncontrolled apoptosis has been considered a major cause of significant immunosuppression. Particularly, apoptosis of lymphocytes, including innate immune cells and adaptive immune cells, is associated with a higher risk of secondary infections and poor outcomes. Multiple postmortem studies have confirmed that sepsis-induced immune cell apoptosis occurs in all age groups, including neonates, pediatric, and adult patients, and it is considered to be a primary contributing factor to the immunosuppressive pathophysiology of sepsis. Therapeutic perspectives targeting apoptosis through various strategies could improve survival in sepsis. In this review article, we will focus on describing the major apoptosis process of immune cells with respect to physiologic and molecular mechanisms. Further, advances in apoptosis-targeted treatment modalities for sepsis will also be discussed.

scholarly journals The Roles of Immune Cells in the Pathogenesis of Fibrosis

2020 ◽  
Vol 21 (15) ◽  
pp. 5203 ◽  
Author(s):  
Enyu Huang ◽  
Na Peng ◽  
Fan Xiao ◽  
Dajun Hu ◽  
Xiaohui Wang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Signaling Pathways ◽  
Immune Cells ◽  
Molecular Mechanisms ◽  
Tissue Injury ◽  
Adaptive Immune ◽  
Recent Advances ◽  
Adaptive Immune Cells ◽  
Stat Signaling ◽  
Fibrotic Diseases

Tissue injury and inflammatory response trigger the development of fibrosis in various diseases. It has been recognized that both innate and adaptive immune cells are important players with multifaceted functions in fibrogenesis. The activated immune cells produce various cytokines, modulate the differentiation and functions of myofibroblasts via diverse molecular mechanisms, and regulate fibrotic development. The immune cells exhibit differential functions during different stages of fibrotic diseases. In this review, we summarized recent advances in understanding the roles of immune cells in regulating fibrotic development and immune-based therapies in different disorders and discuss the underlying molecular mechanisms with a focus on mTOR and JAK-STAT signaling pathways.

scholarly journals Tuning cancer fate: the unremitting role of host immunity

Open Biology ◽  
2017 ◽  
Vol 7 (4) ◽  
pp. 170006 ◽  
Author(s):  
B. Calì ◽  
B. Molon ◽  
A. Viola
Keyword(s):  
Immune Cells ◽  
Immune Cell ◽  
Tumour Progression ◽  
Host Immunity ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Immune Mediated ◽  
Immune Cell Subsets ◽  
Therapeutic Protocols

Host immunity plays a central and complex role in dictating tumour progression. Solid tumours are commonly infiltrated by a large number of immune cells that dynamically interact with the surrounding microenvironment. At first, innate and adaptive immune cells successfully cooperate to eradicate microcolonies of transformed cells. Concomitantly, surviving tumour clones start to proliferate and harness immune responses by specifically hijacking anti-tumour effector mechanisms and fostering the accumulation of immunosuppressive immune cell subsets at the tumour site. This pliable interplay between immune and malignant cells is a relentless process that has been concisely organized in three different phases: elimination, equilibrium and escape. In this review, we aim to depict the distinct immune cell subsets and immune-mediated responses characterizing the tumour landscape throughout the three interconnected phases. Importantly, the identification of key immune players and molecules involved in the dynamic crosstalk between tumour and immune system has been crucial for the introduction of reliable prognostic factors and effective therapeutic protocols against cancers.

scholarly journals Molecular mechanisms governing circulating immune cell heterogeneity across different species revealed by single cell sequencing

2021 ◽  
Author(s):  
Zhibin Li ◽  
chengcheng Sun ◽  
Fei Wang ◽  
Xiran Wang ◽  
Jiacheng Zhu ◽  
...  
Keyword(s):  
Single Cell ◽  
Immune Cells ◽  
Evolutionary Biology ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Cell Types ◽  
Genetic Regulatory Networks ◽  
Peripheral Blood Mononuclear

Background: Immune cells play important roles in mediating immune response and host defense against invading pathogens. However, insights into the molecular mechanisms governing circulating immune cell diversity among multiple species are limited. Methods: In this study, we compared the single-cell transcriptomes of 77 957 immune cells from 12 species using single-cell RNA-sequencing (scRNA-seq). Distinct molecular profiles were characterized for different immune cell types, including T cells, B cells, natural killer cells, monocytes, and dendritic cells. Results: The results revealed the heterogeneity and compositions of circulating immune cells among 12 different species. Additionally, we explored the conserved and divergent cellular cross-talks and genetic regulatory networks among vertebrate immune cells. Notably, the ligand and receptor pair VIM-CD44 was highly conserved among the immune cells. Conclusions: This study is the first to provide a comprehensive analysis of the cross-species single-cell atlas for peripheral blood mononuclear cells (PBMCs). This research should advance our understanding of the cellular taxonomy and fundamental functions of PBMCs, with important implications in evolutionary biology, developmental biology, and immune system disorders

scholarly journals Deregulated immune cell recruitment orchestrated by FOXM1 impairs human diabetic wound healing

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Andrew P. Sawaya ◽  
Rivka C. Stone ◽  
Stephen R. Brooks ◽  
Irena Pastar ◽  
Ivan Jozic ◽  
...  
Keyword(s):  
Wound Healing ◽  
Inflammatory Response ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Diabetic Mouse ◽  
Transcriptional Networks ◽  
Life Threatening ◽  
Diabetic Wound Healing ◽  
Diabetic Wounds

Abstract Diabetic foot ulcers (DFUs) are a life-threatening disease that often result in lower limb amputations and a shortened lifespan. However, molecular mechanisms contributing to the pathogenesis of DFUs remain poorly understood. We use next-generation sequencing to generate a human dataset of pathogenic DFUs to compare to transcriptional profiles of human skin and oral acute wounds, oral as a model of “ideal” adult tissue repair due to accelerated closure without scarring. Here we identify major transcriptional networks deregulated in DFUs that result in decreased neutrophils and macrophages recruitment and overall poorly controlled inflammatory response. Transcription factors FOXM1 and STAT3, which function to activate and promote survival of immune cells, are inhibited in DFUs. Moreover, inhibition of FOXM1 in diabetic mouse models (STZ-induced and db/db) results in delayed wound healing and decreased neutrophil and macrophage recruitment in diabetic wounds in vivo. Our data underscore the role of a perturbed, ineffective inflammatory response as a major contributor to the pathogenesis of DFUs, which is facilitated by FOXM1-mediated deregulation of recruitment of neutrophils and macrophages, revealing a potential therapeutic strategy.

scholarly journals Key Player in Cardiac Hypertrophy, Emphasizing the Role of Toll-Like Receptor 4

2020 ◽  
Vol 7 ◽  
Author(s):  
Zheng Xiao ◽  
Bin Kong ◽  
Hongjie Yang ◽  
Chang Dai ◽  
Jin Fang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Cardiac Hypertrophy ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
New Technologies ◽  
Immune Cell ◽  
Current Knowledge ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Tlr4 Signaling

Toll-like receptor 4 (TLR4), a key pattern recognition receptor, initiates the innate immune response and leads to chronic and acute inflammation. In the past decades, accumulating evidence has implicated TLR4-mediated inflammatory response in regulation of myocardium hypertrophic remodeling, indicating that regulation of the TLR4 signaling pathway may be an effective strategy for managing cardiac hypertrophy's pathophysiology. Given TLR4's significance, it is imperative to review the molecular mechanisms and roles underlying TLR4 signaling in cardiac hypertrophy. Here, we comprehensively review the current knowledge of TLR4-mediated inflammatory response and its interaction ligands and co-receptors, as well as activation of various intracellular signaling. We also describe the associated roles in promoting immune cell infiltration and inflammatory mediator secretion, that ultimately cause cardiac hypertrophy. Finally, we provide examples of some of the most promising drugs and new technologies that have the potential to attenuate TLR4-mediated inflammatory response and prevent or reverse the ominous cardiac hypertrophy outcomes.

scholarly journals Sex differences in neuro(auto)immunity and chronic sciatic nerve pain

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Katja Linher-Melville ◽  
Anita Shah ◽  
Gurmit Singh
Keyword(s):  
Chronic Pain ◽  
Sex Differences ◽  
Immune Cells ◽  
Immune Cell ◽  
Nerve Repair ◽  
Specific Treatment ◽  
Neural Firing ◽  
Biological Sex ◽  
Treatment Regimens ◽  
Nerve Recovery

AbstractChronic pain occurs with greater frequency in women, with a parallel sexually dimorphic trend reported in sufferers of many autoimmune diseases. There is a need to continue examining neuro-immune-endocrine crosstalk in the context of sexual dimorphisms in chronic pain. Several phenomena in particular need to be further explored. In patients, autoantibodies to neural antigens have been associated with sensory pathway hyper-excitability, and the role of self-antigens released by damaged nerves remains to be defined. In addition, specific immune cells release pro-nociceptive cytokines that directly influence neural firing, while T lymphocytes activated by specific antigens secrete factors that either support nerve repair or exacerbate the damage. Modulating specific immune cell populations could therefore be a means to promote nerve recovery, with sex-specific outcomes. Understanding biological sex differences that maintain, or fail to maintain, neuroimmune homeostasis may inform the selection of sex-specific treatment regimens, improving chronic pain management by rebalancing neuroimmune feedback. Given the significance of interactions between nerves and immune cells in the generation and maintenance of neuropathic pain, this review focuses on sex differences and possible links with persistent autoimmune activity using sciatica as an example.

scholarly journals Dysregulation of Systemic Immunity in Aging and Dementia

2021 ◽  
Vol 15 ◽  
Author(s):  
Jenny Lutshumba ◽  
Barbara S. Nikolajczyk ◽  
Adam D. Bachstetter
Keyword(s):  
Immune System ◽  
Immune Cells ◽  
Cell Function ◽  
Immune Cell ◽  
Human Subjects ◽  
Brain Inflammation ◽  
Adaptive Immune Cells ◽  
Age Related ◽  
The Brain ◽  
Age Related Changes

Neuroinflammation and the tissue-resident innate immune cells, the microglia, respond and contribute to neurodegenerative pathology. Although microglia have been the focus of work linking neuroinflammation and associated dementias like Alzheimer’s Disease, the inflammatory milieu of brain is a conglomerate of cross-talk amongst microglia, systemic immune cells and soluble mediators like cytokines. Age-related changes in the inflammatory profile at the levels of both the brain and periphery are largely orchestrated by immune system cells. Strong evidence indicates that both innate and adaptive immune cells, the latter including T cells and B cells, contribute to chronic neuroinflammation and thus dementia. Neurodegenerative hallmarks coupled with more traditional immune system stimuli like infection or injury likely combine to trigger and maintain persistent microglial and thus brain inflammation. This review summarizes age-related changes in immune cell function, with special emphasis on lymphocytes as a source of inflammation, and discusses how such changes may potentiate both systemic and central nervous system inflammation to culminate in dementia. We recap the understudied area of AD-associated changes in systemic lymphocytes in greater detail to provide a unifying perspective of inflammation-fueled dementia, with an eye toward evidence of two-way communication between the brain parenchyma and blood immune cells. We focused our review on human subjects studies, adding key data from animal models as relevant.

scholarly journals Translational Research Studies Unraveling the Origins of Psoriatic Arthritis: Moving Beyond Skin and Joints

2021 ◽  
Vol 8 ◽  
Author(s):  
Janne W. Bolt ◽  
Chaja M. J. van Ansenwoude ◽  
Ihsan Hammoura ◽  
Marleen G. van de Sande ◽  
Lisa G. M. van Baarsen
Keyword(s):  
Psoriatic Arthritis ◽  
Translational Research ◽  
Immune Cells ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Treatment Strategies ◽  
Continuous Treatment ◽  
Adaptive Immune Cells ◽  
Novel Treatment Strategies

Patients with psoriatic arthritis (PsA) are suffering from a decreased quality of life despite currently available treatments. In the latest years, novel therapies targeting the IL-17/IL-23 and TNF pathways improved clinical outcome. Despite this, remission of disease is not achieved in a considerable group of patients, continuous treatment is very often required to reach clinical remission, and prevention of PsA in patients with psoriasis (PsO) is currently impossible. A better understanding of PsA pathogenesis is required to develop novel treatment strategies that target inflammation and destruction more effectively and at an early stage of the disease, or even before clinically manifest disease. The skin is considered as one of the sites of onset of immune activation, triggering the inflammatory cascade in PsA. PsO develops into PsA in 30% of the PsO patients. Influenced by environmental and genetic factors, the inflammatory process in the skin, entheses, and/or gut may evolve into synovial tissue inflammation, characterized by influx of immune cells. The exact role of the innate and adaptive immune cells in disease pathogenesis is not completely known. The involvement of activated IL-17A+ T cells could implicate early immunomodulatory events generated in lymphoid organs thereby shaping the pathogenic inflammatory response leading to disease. In this perspective article, we provide the reader with an overview of the current literature regarding the immunological changes observed during the earliest stages of PsA. Moreover, we will postulate future areas of translational research aimed at increasing our knowledge on the molecular mechanisms driving disease development, which will aid the identification of novel potential therapeutic targets to limit the progression of PsA.

scholarly journals Identification of miRNA-mRNA network and immune-related gene signatures in IgA nephropathy by integrated bioinformatics analysis

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Shi-Yao Wei ◽  
Shuang Guo ◽  
Bei Feng ◽  
Shang-Wei Ning ◽  
Xuan-Yi Du
Keyword(s):  
T Cells ◽  
Iga Nephropathy ◽  
Immune Cells ◽  
Regulatory Network ◽  
Target Genes ◽  
Immune Cell ◽  
Expression Profiles ◽  
Specific Treatment ◽  
Hub Genes ◽  
Ppi Networks

Abstract Background IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide, and its diagnosis depends mainly on renal biopsy. However, there is no specific treatment for IgAN. Moreover, its causes and underlying molecular events require further exploration. Methods The expression profiles of GSE64306 and GSE93798 were downloaded from the Gene Expression Omnibus (GEO) database and used to identify the differential expression of miRNAs and genes, respectively. The StarBase and TransmiR databases were employed to predict target genes and transcription factors of the differentially expressed miRNAs (DE-miRNAs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to predict biological functions. A comprehensive analysis of the miRNA-mRNA regulatory network was constructed, and protein–protein interaction (PPI) networks and hub genes were identified. CIBERSORT was used to examine the immune cells in IgAN, and correlation analyses were performed between the hub genes and infiltrating immune cells. Results Four downregulated miRNAs and 16 upregulated miRNAs were identified. Forty-five and twelve target genes were identified for the upregulated and downregulated DE-miRNAs, respectively. CDKN1A, CDC23, EGR1, HIF1A, and TRIM28 were the hub genes with the highest degrees of connectivity. CIBERSORT revealed increases in the numbers of activated NK cells, M1 and M2 macrophages, CD4 naive T cells, and regulatory T cells in IgAN. Additionally, HIF1A, CDC23, TRIM28, and CDKN1A in IgAN patients were associated with immune cell infiltration. Conclusions A potential miRNA-mRNA regulatory network contributing to IgAN onset and progression was successfully established. The results of the present study may facilitate the diagnosis and treatment of IgAN by targeting established miRNA-mRNA interaction networks. Infiltrating immune cells may play significant roles in IgAN pathogenesis. Future studies on these immune cells may help guide immunotherapy for IgAN patients.

scholarly journals Exosomal delivery of NF-κB inhibitor delays LPS-induced preterm birth and modulates fetal immune cell profile in mouse models

2021 ◽  
Vol 7 (4) ◽  
pp. eabd3865
Author(s):  
Samantha Sheller-Miller ◽  
Enkhtuya Radnaa ◽  
Jae-Kwang Yoo ◽  
Eunsoo Kim ◽  
Kyungsun Choi ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Inflammatory Response ◽  
Immune Cells ◽  
Fluorescent Protein ◽  
Immune Cell ◽  
Innate Immune ◽  
Maternal Inflammation ◽  
Lps Challenge ◽  
Cell Profile ◽  
Fetal Inflammatory Response

Accumulation of immune cells and activation of the pro-inflammatory transcription factor NF-κB in feto-maternal uterine tissues is a key feature of preterm birth (PTB) pathophysiology. Reduction of the fetal inflammatory response and NF-κB activation are key strategies to minimize infection-associated PTB. Therefore, we engineered extracellular vesicles (exosomes) to contain an NF-κB inhibitor, termed super-repressor (SR) IκBα. Treatment with SR exosomes (1 × 1010 per intraperitoneal injection) after lipopolysaccharide (LPS) challenge on gestation day 15 (E15) prolonged gestation by over 24 hours (PTB ≤ E18.5) and reduced maternal inflammation (n ≥ 4). Furthermore, using a transgenic model in which fetal tissues express the red fluorescent protein tdTomato while maternal tissues do not, we report that LPS-induced PTB in mice is associated with influx of fetal innate immune cells, not maternal, into feto-maternal uterine tissues. SR packaged in exosomes provides a stable and specific intervention for reducing the inflammatory response associated with PTB.

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