scholarly journals Loss of self-tolerance leads to altered gene expression and IMD pathway activation in Drosophila melanogaster

2021 ◽  
Author(s):  
Pooja Kr ◽  
Nathan T Mortimer
Keyword(s):  
Drosophila Melanogaster ◽  
Immune System ◽  
Innate Immune ◽  
Loss Of Self ◽  
Imd Pathway ◽  
Immune Mediated ◽  
Pathway Activation ◽  
Self Tolerance ◽  
Ectopic Activation ◽  
Altered Gene

Immune self-tolerance is the ability of a host's immune system to recognize and avoid triggering immune responses against self-tissue. This allows the host to avoid self-directed immune damage while still responding appropriately to pathogen infection. A breakdown of self-tolerance can lead to an autoimmune state in which immune cells target healthy self-tissue, leading to inflammation and tissue damage. In order to better understand the basic biology of autoimmunity and the role of the innate immune system in maintaining self-tolerance, we have recently characterized the Drosophila melanogaster tuSz autoimmune mutant. This mutant strain can serve as a model of innate immune mediated self-tolerance, and here we identify transcripts that are deregulated in flies experiencing a loss of self-tolerance. We found that these changes include the ectopic activation of pro-inflammatory signaling through the Relish/NFκB transcription factor, alterations in transcripts encoding proteins predicted to mediate organismal metabolism, and a downregulation of transcripts linked to developmental processes. This study can provide insight into the transcriptional and physiological changes underlying self-tolerance and autoimmunity.

scholarly journals A Novel Regulatory Player in the Innate Immune System: Long Non-Coding RNAs

2021 ◽  
Vol 22 (17) ◽  
pp. 9535
Author(s):  
Yuhuai Xie ◽  
Yuanyuan Wei
Keyword(s):  
Immune System ◽  
Immune Cells ◽  
Innate Immune System ◽  
Molecular Mechanisms ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Immune Mediated ◽  
Development And Differentiation ◽  
Non Coding Rnas ◽  
And Function

Long non-coding RNAs (lncRNAs) represent crucial transcriptional and post-transcriptional gene regulators during antimicrobial responses in the host innate immune system. Studies have shown that lncRNAs are expressed in a highly tissue- and cell-specific- manner and are involved in the differentiation and function of innate immune cells, as well as inflammatory and antiviral processes, through versatile molecular mechanisms. These lncRNAs function via the interactions with DNA, RNA, or protein in either cis or trans pattern, relying on their specific sequences or their transcriptions and processing. The dysregulation of lncRNA function is associated with various human non-infectious diseases, such as inflammatory bowel disease, cardiovascular diseases, and diabetes mellitus. Here, we provide an overview of the regulation and mechanisms of lncRNA function in the development and differentiation of innate immune cells, and during the activation or repression of innate immune responses. These elucidations might be beneficial for the development of therapeutic strategies targeting inflammatory and innate immune-mediated diseases.

scholarly journals Convergent Evolution by Cancer and Viruses in Evading the NKG2D Immune Response

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3827
Author(s):  
Richard Baugh ◽  
Hena Khalique ◽  
Leonard W. Seymour
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Cancer Cells ◽  
Innate Immune System ◽  
Cell Transformation ◽  
Innate Immune ◽  
Immune Mediated ◽  
Pathogenic Viruses ◽  
Group 2 ◽  
Immune Defences

The natural killer group 2 member D (NKG2D) receptor and its family of NKG2D ligands (NKG2DLs) are key components in the innate immune system, triggering NK, γδ and CD8+ T cell-mediated immune responses. While surface NKG2DL are rarely found on healthy cells, expression is significantly increased in response to various types of cellular stress, viral infection, and tumour cell transformation. In order to evade immune-mediated cytotoxicity, both pathogenic viruses and cancer cells have evolved various mechanisms of subverting immune defences and preventing NKG2DL expression. Comparisons of the mechanisms employed following virus infection or malignant transformation reveal a pattern of converging evolution at many of the key regulatory steps involved in NKG2DL expression and subsequent immune responses. Exploring ways to target these shared steps in virus- and cancer-mediated immune evasion may provide new mechanistic insights and therapeutic opportunities, for example, using oncolytic virotherapy to re-engage the innate immune system towards cancer cells.

Innate Immune Mechanisms of Arterial Hypertension and Autoimmune Disease

2020 ◽  
Author(s):  
Rebecca Jung ◽  
Johannes Wild ◽  
Julia Ringen ◽  
Susanne Karbach ◽  
Philip Wenzel
Keyword(s):  
Blood Pressure ◽  
Immune System ◽  
Arterial Hypertension ◽  
Immune Cells ◽  
Vascular Dysfunction ◽  
Review Article ◽  
Innate Immune ◽  
Immune Mediated ◽  
The Central Nervous System ◽  
Relationship Of

Abstract The immune system is indispensable in the development of vascular dysfunction and hypertension. The interplay between immune cells and the vasculature, kidneys, heart, and blood pressure regulating nuclei in the central nervous system results in a complex and closely interwoven relationship of the immune system with arterial hypertension. A better understanding of this interplay is necessary for optimized and individualized antihypertensive therapy. Our review article focuses on innate cells in hypertension and to what extent they impact on development and preservation of elevated blood pressure. Moreover, we address the association of hypertension with chronic autoimmune diseases. The latter are ideally suited to learn about immune-mediated mechanisms in cardiovascular disease leading to high blood pressure.

scholarly journals Interleucina-17 como Alvo Terapêutico na Psoríase

2014 ◽  
Vol 27 (2) ◽  
pp. 252 ◽  
Author(s):  
Tiago Torres ◽  
Paulo Filipe
Keyword(s):  
Immune System ◽  
Th17 Cells ◽  
Clinical Results ◽  
Biologic Agents ◽  
Innate Immune ◽  
New Drugs ◽  
Immune Mediated ◽  
Attractive Therapeutic Target ◽  
Effector Cytokines ◽  
Near Future

Psoriasis is a chronic, immune-mediated inflammatory disease that affects up to 1-3% of the general population. An advanced understanding of the immune-pathogenesis of psoriasis has led to the development of new drugs that refine existing treatments or target novel molecular and immunologic pathways. IL-17 and Th17 cells play an important role in the pathogenesis of several autoimmune and immune-mediated disorders, including psoriasis. IL-17A, a pro-inflammatory cytokine, is produced by Th17 cells along with other effector cytokines, such as IL-17F an IL-22, but it is also expressed by other cells of the innate immune system, including mast cells, neutrophils or dendritic cells, that are found in psoriatic lesions. For this reason IL-17 has emerged as an attractive therapeutic target. Agents that inhibit IL-17 are in development and preliminary clinical results are promising, confirming the importance of IL-17 in psoriasis<br />pathophysiology. Their selective intervention in the immune system makes them an attractive therapeutic approach to autoimmune diseases, particularly psoriasis, being possible that in the near future these novel therapies could be a valid alternative for currently available biologic agents.

Innate Immune-mediated Antiviral Response to SARS-CoV-2 and Convalescent sera a potential Prophylactic and Therapeutic Agent to Tackle COVID-19 (Preprint)

2020 ◽  
Author(s):  
Abdullah Abdullah ◽  
Shah Faisal
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Viral Replication ◽  
Innate Immune System ◽  
Passive Immunization ◽  
Innate Immune ◽  
Alveolar Cells ◽  
Experimental Drugs ◽  
Immune Mediated

UNSTRUCTURED The whole world is confronting the pandemic of SARS-CoV-2. And unfortunately there is no vaccine to prevent from novel coronavirus infection. Beside several experimental drugs, the strong immune responses and convalescent sera are the current two potential options to tackle COVID-19 infection. When the virus get enter into the lungs the innate immune system activated. Innate immune-mediated antiviral responses is initiated by the recognition of viral invasion through PAMPs. In coronavirus the pathogen associated molecular patterns are recognized by toll like receptors (TLR-3 & 7), endosomal ribonucleic acid receptors, RNA in cytosol and by pattern recognition receptor (PRR RIG-1) in the alveolar cells and site of invasion. Nuclear factor (NF-κB) and interferon regulatory transcription factor (IRF3) are activated in response to above recognition episode and translocate to nucleus. These transcription factors in the nucleus initiate the expression of interferon type 1 and pro-inflammatory cytokine storm, which leads to first line of defense at site of viral entrance. The effectiveness of innate immune system greatly relies on type 1 interferon’s and its cascade, because of their role in inhibition of viral replication and initiation of adaptive immune responses. The successful interferon type 1 response put down the viral replication and transmission at prompt point. Passive immunization is the administering of antibodies into infected patients which is taken from recovered individuals. The convalescent sera of the recovered COVID-19 patients contains antiviral neutralizing antibodies and used for the purpose of prophylaxis in exposed and therapeutically in infected individuals by SARS-CoV-2. The convalescent sera is found effective when administered early at the onset of symptoms.

scholarly journals Immune-mediated vincristine-induced neuropathy: Unlocking therapies

2021 ◽  
Vol 218 (5) ◽  
Author(s):  
Masha G. Savelieff ◽  
Eva L. Feldman
Keyword(s):  
Immune System ◽  
Peripheral Neuropathy ◽  
Cancer Patients ◽  
Innate Immune System ◽  
Innate Immune ◽  
Immune System Activation ◽  
Immune Mediated ◽  
System Activation ◽  
Effective Treatments

Vincristine-induced peripheral neuropathy (VIPN) is a prevalent and painful complication in cancer patients that lacks effective treatments. In this issue of JEM, Starobova et al. (2021. J. Exp. Med.https://doi.org/10.1084/jem.20201452) report that VIPN is driven by innate immune system activation, a discovery that unlocks immunotherapies as potential treatments.

scholarly journals Molecular Pathogenesis of Anti-NMDAR Encephalitis

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Hao Ding ◽  
Zhihong Jian ◽  
Creed M. Stary ◽  
Wei Yi ◽  
Xiaoxing Xiong
Keyword(s):  
Autoimmune Disease ◽  
Molecular Mechanisms ◽  
Cellular Transformation ◽  
Diagnostic Methods ◽  
Loss Of Self ◽  
Nmdar Encephalitis ◽  
Immune Mediated ◽  
Self Tolerance ◽  
Nmda Glutamate Receptors ◽  
Diagnostic Approaches

Anti-NMDAR encephalitis is a recently identified autoimmune disease, described by an immune-mediated loss of NMDA glutamate receptors, resulting in progressive mental deterioration. To date, literature on anti-NMDAR encephalitis has been largely clinically oriented, including descriptions of the clinical presentation and course, diagnostic methods, and potential clinical treatments. However, the underlying molecular mechanisms contributing to the complex immunological cellular transformation that is associated with the progression of anti-NMDAR encephalitis remain to be adequately explored. This review will provide a summary of the current literature on anti-NMDAR encephalitis, including the immunologic molecular mechanisms contributing to disease progression. In particular this review will focus on the effect of anti-NMDAR on GluN2-NMDAR expression and the molecular transformation of B and T leukocytes in the loss of self-tolerance. Further research on the immunologic mechanisms contributing to anti-NMDAR encephalitis may provide an avenue for future novel diagnostic approaches, such as immunologic surveillance, as well as new therapeutic strategies for this recently identified autoimmune disease.

scholarly journals The innate immune systems of malacostracan crustaceans exhibit both conserved and evolutionarily distinct components

2016 ◽  
Author(s):  
Alvina G. Lai ◽  
A. Aziz Aboobaker
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Large Scale ◽  
Gene Families ◽  
Innate Immune ◽  
Divergent Evolution ◽  
Future Research ◽  
Immune Gene ◽  
Scale Production ◽  
Imd Pathway

AbstractGrowing demands for aquatic sources of animal proteins have attracted significant investments in aquaculture research in recent years. The crustacean aquaculture industry has undergone substantial growth to accommodate a rising global demand, however such large-scale production is susceptible to pathogen-mediated destruction. It is clear that a thorough understanding of the crustacean innate immune system is imperative for future research into combating current and future pathogens of the main food crop species. Through a comparative genomics approach utilising extant data from 55 species, we describe the innate immune system of crustaceans from the Malacostraca class. We identify 7407 malacostracan genes from 39 gene families implicated in different aspects of host defence and demonstrate dynamic evolution of innate immunity components within this group. Malacostracans have achieved flexibility in recognising infectious agents through divergent evolution and expansion of pathogen recognition receptors genes. Antiviral RNAi, Toll and JAK-STAT signal transduction pathways have remained conserved within Malacostraca, although the Imd pathway appears to lack several key components. Immune effectors such as the antimicrobial peptides (AMPs) have unique evolutionary profiles, with many malacostracan AMPs not found in other arthropod groups. Lastly, we describe four putative novel immune gene families, characterised by distinct protein domains, potentially representing important evolutionary novelties of the malacostracan immune system.

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