scholarly journals Role of Vanadium in Cellular and Molecular Immunology: Association with Immune-Related Inflammation and Pharmacotoxicology Mechanisms

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Olga Tsave ◽  
Savvas Petanidis ◽  
Efrosini Kioseoglou ◽  
Maria P. Yavropoulou ◽  
John G. Yovos ◽  
...  
Keyword(s):  
Immune Responses ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Chemical Reactivity ◽  
Inflammatory Cells ◽  
T Cell Signaling ◽  
Cell Immunotherapy ◽  
Molecular Immunology ◽  
Anti Inflammatory

Over the last decade, a diverse spectrum of vanadium compounds has arisen as anti-inflammatory therapeutic metallodrugs targeting various diseases. Recent studies have demonstrated that select well-defined vanadium species are involved in many immune-driven molecular mechanisms that regulate and influence immune responses. In addition, advances in cell immunotherapy have relied on the use of metallodrugs to create a “safe,” highly regulated, environment for optimal control of immune response. Emerging findings include optimal regulation of B/T cell signaling and expression of immune suppressive or anti-inflammatory cytokines, critical for immune cell effector functions. Furthermore, in-depth perusals have explored NF-κB and Toll-like receptor signaling mechanisms in order to enhance adaptive immune responses and promote recruitment or conversion of inflammatory cells to immunodeficient tissues. Consequently, well-defined vanadium metallodrugs, poised to access and resensitize the immune microenvironment, interact with various biomolecular targets, such as B cells, T cells, interleukin markers, and transcription factors, thereby influencing and affecting immune signaling. A synthetically formulated and structure-based (bio)chemical reactivity account of vanadoforms emerges as a plausible strategy for designing drugs characterized by selectivity and specificity, with respect to the cellular molecular targets intimately linked to immune responses, thereby giving rise to a challenging field linked to the development of immune system vanadodrugs.

scholarly journals Selenium, Selenoproteins, and Immunity

Nutrients ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1203 ◽  
Author(s):  
Joseph Avery ◽  
Peter Hoffmann
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
High Throughput ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Biological Effects ◽  
Cell Functions ◽  
Experimental Systems ◽  
Physiological Processes

Selenium is an essential micronutrient that plays a crucial role in development and a wide variety of physiological processes including effect immune responses. The immune system relies on adequate dietary selenium intake and this nutrient exerts its biological effects mostly through its incorporation into selenoproteins. The selenoproteome contains 25 members in humans that exhibit a wide variety of functions. The development of high-throughput omic approaches and novel bioinformatics tools has led to new insights regarding the effects of selenium and selenoproteins in human immuno-biology. Equally important are the innovative experimental systems that have emerged to interrogate molecular mechanisms underlying those effects. This review presents a summary of the current understanding of the role of selenium and selenoproteins in regulating immune cell functions and how dysregulation of these processes may lead to inflammation or immune-related diseases.

scholarly journals Interleukin-27 and Its Diverse Effects on Bacterial Infections

2021 ◽  
Vol 12 ◽  
Author(s):  
Yugo Morita ◽  
Elysia A. Masters ◽  
Edward M. Schwarz ◽  
Gowrishankar Muthukrishnan
Keyword(s):  
Immune Responses ◽  
Bacterial Infections ◽  
Immune Cell ◽  
Chronic Infections ◽  
Cell Functions ◽  
Interleukin 27 ◽  
Life Threatening ◽  
Anti Inflammatory ◽  
Active Research

Innate and adaptive immune responses against pathogens are known to be carefully orchestrated by specific cytokines that initiate and down regulate immune cell functions from the initial infection through tissue repair and homeostasis. However, some cytokines, including interleukin-27, are expressed at multiple phases of the infection, such that their pro and anti-inflammatory functions have been difficult to interpret. As elucidation of specific cytokine functions throughout infection is central to our understanding of protective vs. susceptible immunity and return to homeostasis vs. prolonged inflammation leading to septic shock, here we review the literature on IL-27 signaling and the various functions of this heterodimeric ligand member of the IL-12 cytokine family. Canonically, IL-27 is produced by antigen-presenting cells, and is thought of as an immunostimulatory cytokine due to its capacity to induce Th1 differentiation. However, many studies have also identified various immunosuppressive effects of IL-27 signaling, including suppression of Th17 differentiation and induction of co-inhibitory receptors on T cells. Thus, the exact role of IL-27 in the context of infectious diseases remains a topic of debate and active research. Additionally, as recent interest has focused on clinical management of acute vs. chronic infections, and life-threatening “cytokine storm” from sepsis, we propose a hypothetical model to explain the biphasic role of IL-27 during the early and late phases of immune responses to reconcile its known pro and anti-inflammatory functions, which could be therapeutically regulated to improve patient outcomes of infection.

scholarly journals The SARS-CoV-2/Receptor Axis in Heart and Blood Vessels: A Crisp Update on COVID-19 Disease with Cardiovascular Complications

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1346
Author(s):  
Priya Veluswamy ◽  
Max Wacker ◽  
Dimitrios Stavridis ◽  
Thomas Reichel ◽  
Hendrik Schmidt ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Immune Cell ◽  
Cardiovascular Complications ◽  
World Health ◽  
Endothelial Glycocalyx ◽  
Pathological State ◽  
Mediated Action ◽  
Cell Responses ◽  
Health Organization

The SARS-CoV-2 virus causing COVID-19 disease has emerged expeditiously in the world and has been declared pandemic since March 2020, by World Health Organization (WHO). The destructive effects of SARS-CoV-2 infection are increased among the patients with pre-existing chronic conditions and, in particular, this review focuses on patients with underlying cardiovascular complications. The expression pattern and potential functions of SARS-CoV-2 binding receptors and the attributes of SARS-CoV-2 virus tropism in a physio-pathological state of heart and blood vessel are precisely described. Of note, the atheroprotective role of ACE2 receptors is reviewed. A detailed description of the possible detrimental role of SARS-CoV-2 infection in terms of vascular leakage, including endothelial glycocalyx dysfunction and bradykinin 1 receptor stimulation is concisely stated. Furthermore, the potential molecular mechanisms underlying SARS-CoV-2 induced clot formation in association with host defense components, including activation of FXIIa, complements and platelets, endothelial dysfunction, immune cell responses with cytokine-mediated action are well elaborated. Moreover, a brief clinical update on patient with COVID-19 disease with underlying cardiovascular complications and those who had new onset of cardiovascular complications post-COVID-19 disease was also discussed. Taken together, this review provides an overview of the mechanistic aspects of SARS-CoV-2 induced devastating effects, in vital organs such as the heart and vessels.

scholarly journals miR-146a is a significant brake on autoimmunity, myeloproliferation, and cancer in mice

2011 ◽  
Vol 208 (6) ◽  
pp. 1189-1201 ◽  
Author(s):  
Mark P. Boldin ◽  
Konstantin D. Taganov ◽  
Dinesh S. Rao ◽  
Lili Yang ◽  
Jimmy L. Zhao ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Immune Cell ◽  
Myeloid Cell ◽  
Genetically Engineered ◽  
Biological Processes ◽  
Targeted Deletion ◽  
Genetically Engineered Mice ◽  
Immune Defects ◽  
Molecular Brake

Excessive or inappropriate activation of the immune system can be deleterious to the organism, warranting multiple molecular mechanisms to control and properly terminate immune responses. MicroRNAs (miRNAs), ∼22-nt-long noncoding RNAs, have recently emerged as key posttranscriptional regulators, controlling diverse biological processes, including responses to non-self. In this study, we examine the biological role of miR-146a using genetically engineered mice and show that targeted deletion of this gene, whose expression is strongly up-regulated after immune cell maturation and/or activation, results in several immune defects. Collectively, our findings suggest that miR-146a plays a key role as a molecular brake on inflammation, myeloid cell proliferation, and oncogenic transformation.

scholarly journals Emerging Role of Exosomes in Tuberculosis: From Immunity Regulations to Vaccine and Immunotherapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Yin-Fu Sun ◽  
Jiang Pi ◽  
Jun-Fa Xu
Keyword(s):  
Immune Responses ◽  
Delivery System ◽  
Immune Modulation ◽  
Immune Cell ◽  
Critical Role ◽  
Cell Communication ◽  
Immune Defense ◽  
Research Progress ◽  
Recent Research Progress

Exosomes are cell-derived nanovesicles carrying protein, lipid, and nucleic acid for secreting cells, and act as significant signal transport vectors for cell-cell communication and immune modulation. Immune-cell-derived exosomes have been found to contain molecules involved in immunological pathways, such as MHCII, cytokines, and pathogenic antigens. Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), remains one of the most fatal infectious diseases. The pathogen for tuberculosis escapes the immune defense and continues to replicate despite rigorous and complicate host cell mechanisms. The infected-cell-derived exosomes under this circumstance are found to trigger different immune responses, such as inflammation, antigen presentation, and activate subsequent pathways, highlighting the critical role of exosomes in anti-MTB immune response. Additionally, as a novel kind of delivery system, exosomes show potential in developing new vaccination and treatment of tuberculosis. We here summarize recent research progress regarding exosomes in the immune environment during MTB infection, and further discuss the potential of exosomes as delivery system for novel anti-MTB vaccines and therapies.

scholarly journals 641 Spatially organized multicellular immune hubs in MMRd and MMRp colorectal cancer

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A670-A670
Author(s):  
Jonathan Chen ◽  
Karin Pelka ◽  
Matan Hofree ◽  
Marios Giannakis ◽  
Genevieve Boland ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Mismatch Repair ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Single Cells ◽  
Large Set ◽  
Colon Tissue

BackgroundImmune responses to cancer are highly variable, with DNA mismatch repair-deficient (MMRd) tumors exhibiting more anti-tumor immunity than mismatch repair-proficient (MMRp) tumors. Almost all tumors are infiltrated with immune cells, but the types of immune responses and their effects on tumor growth, metastasis and death, vary greatly between different cancers and individual tumors. Which of the numerous cell subsets in a tumor contribute to the response, how their interactions are regulated, and how they are spatially organized within tumors remains poorly understood.MethodsTo understand the rules governing these varied responses, we transcriptionally profiled 371,223 single cells from colorectal tumors and adjacent normal tissues of 28 MMRp and 34 MMRd treatment-naive patients. We developed a systematic approach to discover cell types, their underlying gene programs, and cellular communities based on single cell RNA-seq (scRNAseq) profiles and applied it to study the distinguishing features of human MMRd and MMRp colorectal cancer. Cellular communities discovered from this analysis were spatially mapped in tissue sections using multiplex RNA in situ hybridization microscopy.ResultsTo understand the basis for differential immune responses in CRC, we first determined and compared the immune cell composition of MMRd and MMRp CRC and normal colon tissue, finding dramatic remodeling between tumor and normal tissue and between MMRd and MMRp tumors, particularly within the myeloid, T cell, and stromal compartments. Among the clusters enriched in MMRd tumors were activated CXCL13+ CD8 T cells. Importantly, gene program co-variation analysis revealed multicellular networks. We discovered a myeloid cell-attracting hub at the tumor-luminal interface associated with tissue damage, and an MMRd-enriched immune hub within the tumor, with activated IFNG+ and CXCL13+ T cells together with malignant and myeloid cells expressing T-cell-attracting chemokines (figure 1).ConclusionsOur study provides a rich dataset of cellular states, gene programs and their transformations in tumors across a relatively large cohort of patients with colorectal cancer. Our predictions of several multicellular hubs based on co-variation of gene expression programs, and subsequent spatial localization of two major immune-malignant hubs, organizes a large set of cell states and programs into a smaller number of coordinated networks of cells and processes. Understanding the molecular mechanisms underlying these hubs, and studying their temporal and spatial regulation upon treatment will be critical for advancing cancer therapy.Ethics ApprovalThis study was approved by the DF-HCC institutional review board (protocols 03-189 and 02-240).Abstract 641 Figure 1A coordinated network of CXCL13+ T cells with myeloid and malignant cells expressing ISGs. Image shows a portion of formalin-fixed paraffin-embedded tissue from an MMRd CRC specimen stained with multiplex RNA ISH / IF for PanCK-IF, CD3E-ISH, CXCL10/CXCL11-ISH, CXCL13-ISH, and IFNG-ISH. Note IFNG+ and CXCL13+ cells in proximity to cells expressing the chemokines CXCL10/CXCL11

scholarly journals Neuroinflammation and Its Impact on the Pathogenesis of COVID-19

2021 ◽  
Vol 8 ◽  
Author(s):  
Mohammed M. Almutairi ◽  
Farzane Sivandzade ◽  
Thamer H. Albekairi ◽  
Faleh Alqahtani ◽  
Luca Cucullo
Keyword(s):  
Immune System ◽  
Molecular Mechanisms ◽  
Potential Role ◽  
Immune Cell ◽  
Clinical Manifestations ◽  
Cell Infiltration ◽  
Cellular Mechanisms ◽  
Cytokine Levels

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The clinical manifestations of COVID-19 include dry cough, difficult breathing, fever, fatigue, and may lead to pneumonia and respiratory failure. There are significant gaps in the current understanding of whether SARS-CoV-2 attacks the CNS directly or through activation of the peripheral immune system and immune cell infiltration. Although the modality of neurological impairments associated with COVID-19 has not been thoroughly investigated, the latest studies have observed that SARS-CoV-2 induces neuroinflammation and may have severe long-term consequences. Here we review the literature on possible cellular and molecular mechanisms of SARS-CoV-2 induced-neuroinflammation. Activation of the innate immune system is associated with increased cytokine levels, chemokines, and free radicals in the SARS-CoV-2-induced pathogenic response at the blood-brain barrier (BBB). BBB disruption allows immune/inflammatory cell infiltration into the CNS activating immune resident cells (such as microglia and astrocytes). This review highlights the molecular and cellular mechanisms involved in COVID-19-induced neuroinflammation, which may lead to neuronal death. A better understanding of these mechanisms will help gain substantial knowledge about the potential role of SARS-CoV-2 in neurological changes and plan possible therapeutic intervention strategies.

scholarly journals The RIG-I Signal Pathway Mediated Panax notoginseng Saponin Anti-Inflammatory Effect in Ischemia Stroke

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Chujun Zhang ◽  
Sai Zhang ◽  
Lanxiang Wang ◽  
Soyeon Kang ◽  
Jiabao Ma ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Molecular Mechanisms ◽  
Chinese Herb ◽  
Inflammatory Cells ◽  
Panax Notoginseng ◽  
Artery Occlusion ◽  
Blue Staining ◽  
Bioactive Constituents ◽  
Anti Inflammatory ◽  
Cerebral Artery Occlusion

Panax notoginseng saponins (PNS), the main bioactive constituents of a traditional Chinese herb Panax notoginseng, were commonly used for ischemic stroke in China. However, the associated cellular and molecular mechanisms of PNS have not been well examined. This study aimed to decipher the underlying molecular target of PNS in the treatment of cerebral ischemia. The oxygen-glucose-deprived (OGD) model of rat brain microvascular endothelial cells (BMECs) was used in this study. The alteration of gene expression in rat BMECs after PNS treatment was measured by microarray and indicated that there were 38 signaling pathways regulated by PNS. Among them, RIG-I receptor and related signaling molecules TNF receptor-associated factor 2 (Traf2) and nuclear factor-kappa B (NF-κB) were significantly suppressed by PNS, which was verified again in OGD-induced BMECs measured by FQ-PCR and western blotting and in middle cerebral artery occlusion (MCAO) rats measured by immunohistochemistry. The levels of TNF-α, IL-8, and the downstream cytokines regulated by RIG-I receptor pathway were also decreased by PNS. Meanwhile, the neurological evaluation, hematoxylin and eosin (HE) staining, and Evans blue staining were conducted to evaluate the effect of PNS in MCAO rats. Results showed PNS significantly improved functional outcome and cerebral vascular leakage. Flow cytometry showed the number of the inflammatory cells infiltrated in brain tissue was decreased in PNS treatment. Our results identified that RIG-I signaling pathway mediated anti-inflammatory properties of PNS in cerebral ischemia, which provided the novel insights of PNS application in clinics.

scholarly journals A functional spleen contributes to afucosylated IgG in humans

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Iwona Wojcik ◽  
David E. Schmidt ◽  
Lisa A. de Neef ◽  
Minke A. E. Rab ◽  
Bob Meek ◽  
...  
Keyword(s):  
Immune Responses ◽  
Viral Infections ◽  
Immune Cell ◽  
Lymphoid Organ ◽  
Immune Effector ◽  
Adaptive Immune ◽  
Wide Range ◽  
Humoral Responses ◽  
First Time

AbstractAs a lymphoid organ, the spleen hosts a wide range of immune cell populations, which not only remove blood-borne antigens, but also generate and regulate antigen-specific immune responses. In particular, the splenic microenvironment has been demonstrated to play a prominent role in adaptive immune responses to enveloped viral infections and alloantigens. During both types of immunizations, antigen-specific immunoglobulins G (IgGs) have been characterized by the reduced amount of fucose present on N-linked glycans of the fragment crystallizable (Fc) region. These glycans are essential for mediating the induction of immune effector functions. Therefore, we hypothesized that a spleen may modulate humoral responses and serve as a preferential site for afucosylated IgG responses, which potentially play a role in immune thrombocytopenia (ITP) pathogenesis. To determine the role of the spleen in IgG-Fc glycosylation, we performed IgG subclass-specific liquid chromatography–mass spectrometry (LC–MS) analysis of Fc glycosylation in a large cohort of individuals splenectomized due to trauma, due to ITP, or spherocytosis. IgG-Fc fucosylation was consistently increased after splenectomy, while no effects for IgG-Fc galactosylation and sialylation were observed. An increase in IgG1- and IgG2/3-Fc fucosylation level upon splenectomy has been reported here for the first time, suggesting that immune responses occurring in the spleen may be particularly prone to generate afucosylated IgG responses. Surprisingly, the level of total IgG-Fc fucosylation was decreased in ITP patients compared to healthy controls. Overall, our results suggest a yet unrecognized role of the spleen in either the induction or maintenance of afucosylated IgG responses by B cells.

Abstract WMP73: Peripheral T Cells From MCAO Mice Contribute to Microglial Polarization

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Dan Ye ◽  
Yun Xu
Keyword(s):  
T Cells ◽  
Th17 Cells ◽  
Inflammatory Cells ◽  
Treg Cells ◽  
Experimental Stroke ◽  
Dual Roles ◽  
Microglial Polarization ◽  
Peripheral T Cells ◽  
Anti Inflammatory

Both resident microglia and infiltrated peripheral T cells have been proved to play important roles in the pathology of stroke. It is well accepted that activated microglia exert dual roles, including pro-inflammatory (M1) and anti-inflammatory (M2) functions. However, the mechanism regulating microglial polarization remains elusive. T cells are recruited into the ischemic area within 24 h after stroke, which also exhibit pro-inflammatory (Th1, Th17) and anti-inflammatory (Th2, Treg) functions. The interaction between microglia and T cells after stroke is barely understood, which may be served as modifiers of pathobiology in stroke. Here we described the role of T cells in the microglial polarization in mouse experimental stroke. We isolated T cells from spleens of MCAO mice at 24 h and 72 h, respectively, and then added to cultured microglia for 24 h. Our results indicated that splenic T cells obtained at 24 h after MCAO selectively promoted microglia polarize to a pro-inflammatory (M1) state, while T cells obtained at 72 h, favored microglia polarize to an anti-inflammatory (M2) state. The results of flow cytometry showed that Th1 and Th17 cells increased at 24 h after MCAO while Th2 and Treg cells increased at 72 h after MCAO. This study implicates that distinct subtypes of T cells contribute differentially to microglial polarization after stroke onset. Therefore, treatments aiming at modulating the ratios of T cells to anti-inflammatory cells have the potential to induce microglial polarize to M2 phenotype and improve the outcome of ischemic stroke.

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