Could the Heat Shock Proteins 70 Family Members Exacerbate the Immune Response in Multiple Sclerosis? An in Silico Study

Chiricosta, Luigi; Bramantı, Placido; Mazzon, Emanuela

doi:10.3390/genes11060615

Cited by 20 publications

(17 citation statements)

References 56 publications

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“…Corpus callosum and optic chiasm were the most significantly affected CNS regions in a study, and myelinating oligodendrocytes were most enriched with differentially expressed genes ( 51 ). Heat shock proteins were upregulated in all examined brain regions ( HSPA1A, HSPA1B, HSPA7, HSPA6, HSPH1, HSPA4L ) ( 52 ). Genes important in antigen-presentation, inflammation and hypoxia-induced responses were altered in the corpus callosum and optic chiasm ( TAPBP, IRF4, CTSB, CD79A ), while STAT6 and HLA-DRB5 were only increased in the optic chiasm.…”

Section: Resultsmentioning

confidence: 99%

A Systematic Review of Tissue and Single Cell Transcriptome/Proteome Studies of the Brain in Multiple Sclerosis

Elkjaer

Röttger

Baumbach³

et al. 2022

Front. Immunol.

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Multiple sclerosis (MS) is an inflammatory demyelinating and degenerative disease of the central nervous system (CNS). Although inflammatory responses are efficiently treated, therapies for progression are scarce and suboptimal, and biomarkers to predict the disease course are insufficient. Cure or preventive measures for MS require knowledge of core pathological events at the site of the tissue damage. Novelties in systems biology have emerged and paved the way for a more fine-grained understanding of key pathological pathways within the CNS, but they have also raised questions still without answers. Here, we systemically review the power of tissue and single-cell/nucleus CNS omics and discuss major gaps of integration into the clinical practice. Systemic search identified 49 transcriptome and 11 proteome studies of the CNS from 1997 till October 2021. Pioneering molecular discoveries indicate that MS affects the whole brain and all resident cell types. Despite inconsistency of results, studies imply increase in transcripts/proteins of semaphorins, heat shock proteins, myelin proteins, apolipoproteins and HLAs. Different lesions are characterized by distinct astrocytic and microglial polarization, altered oligodendrogenesis, and changes in specific neuronal subtypes. In all white matter lesion types, CXCL12, SCD, CD163 are highly expressed, and STAT6- and TGFβ-signaling are increased. In the grey matter lesions, TNF-signaling seems to drive cell death, and especially CUX2-expressing neurons may be susceptible to neurodegeneration. The vast heterogeneity at both cellular and lesional levels may underlie the clinical heterogeneity of MS, and it may be more complex than the current disease phenotyping in the clinical practice. Systems biology has not solved the mystery of MS, but it has discovered multiple molecules and networks potentially contributing to the pathogenesis. However, these results are mostly descriptive; focused functional studies of the molecular changes may open up for a better interpretation. Guidelines for acceptable quality or awareness of results from low quality data, and standardized computational and biological pipelines may help to overcome limited tissue availability and the “snap shot” problem of omics. These may help in identifying core pathological events and point in directions for focus in clinical prevention.

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Section: Resultsmentioning

confidence: 99%

A Systematic Review of Tissue and Single Cell Transcriptome/Proteome Studies of the Brain in Multiple Sclerosis

Elkjaer

Röttger

Baumbach³

et al. 2022

Front. Immunol.

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“…HSPs are important proteins commonly found as chaperones that mediate the correct assembly of proteins and their intracellular location to protect other proteins against chemical and physical changes in the cytoplasm ( Lanneau et al, 2008 ). HSPs constitute approximately 5–10% of the total protein of all normal unstressed cells, perform many constitutive stabilization state functions, and play an important role in maintaining cell homeostasis ( Chiricosta et al, 2020 ). In stress-free cells, HSPs play various instinctive functions.…”

Section: Resultsmentioning

confidence: 99%

Copper Tolerance Mechanism of the Novel Marine Multi-Stress Tolerant Yeast Meyerozyma guilliermondii GXDK6 as Revealed by Integrated Omics Analysis

Yan

Sun

et al. 2021

Front. Microbiol.

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Various agricultural products used in food fermentation are polluted by heavy metals, especially copper, which seriously endangers human health. Methods to remove copper with microbial strategies have gained interests. A novel Meyerozyma guilliermondii GXDK6 could survive independently under high stress of copper (1400 ppm). The copper tolerance mechanism of GXDK6 was revealed by integrated omics in this work. Whole-genome analysis showed that nine genes (i.e., CCC2, CTR3, FRE2, GGT, GST, CAT, SOD2, PXMP4, and HSP82) were related to GXDK6 copper tolerance. Copper stress elevated glutathione metabolism-related gene expression, glutathione content, and glutathione sulfur transferase activity, suggesting enhanced copper conjugation and detoxification in cells. The inhibited copper uptake by Ctr3 and enhanced copper efflux by Ccc2 contributed to the decrease in intracellular copper concentration. The improved expression of antioxidant enzyme genes (PXMP4, SOD2, and CAT), accompanied by the enhanced activities of antioxidant enzymes (peroxidase, superoxide dismutase, and catalase), decreased copper-induced reactive oxygen species production, protein carbonylation, lipid peroxidation, and cell death. The metabolite D-mannose against harsh stress conditions was beneficial to improving copper tolerance. This study contributed to understanding the copper tolerance mechanism of M. guilliermondii and its application in removing copper during fermentation.

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“…Immunoproteomic analysis showed that GroEL and DnaK were among the chaperones in C. jejuni that share high homology with human homologues that may contribute to Guillain-Barré syndrome triggering [ 95 ]. Recently, it was speculated that HSP70 may play a role in the autoimmune disease multiple sclerosis (MS) as genes related to HSP70 were overexpressed in MS patients [ 96 ]. A rather elegant study by Elfaitouri et al demonstrated that there may be cross-reactivity between prokaryotic HSP60 and antibodies derived from patients with the autoimmune disease myalgic encephalomyelitis.…”

Section: Evidence For Adjuvant and Immunomodulatory Potential Of Pmentioning

confidence: 99%

Understanding GroEL and DnaK Stress Response Proteins as Antigens for Bacterial Diseases

Fourie

Wilson

2020

Vaccines

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Bacteria do not simply express a constitutive panel of proteins but they instead undergo dynamic changes in their protein repertoire in response to changes in nutritional status and when exposed to different environments. These differentially expressed proteins may be suitable to use for vaccine antigens if they are virulence factors. Immediately upon entry into the host organism, bacteria are exposed to a different environment, which includes changes in temperature, osmotic pressure, pH, etc. Even when an organism has already penetrated the blood or lymphatics and it then enters another organ or a cell, it can respond to these new conditions by increasing the expression of virulence factors to aid in bacterial adherence, invasion, or immune evasion. Stress response proteins such as heat shock proteins and chaperones are some of the proteins that undergo changes in levels of expression and/or changes in cellular localization from the cytosol to the cell surface or the secretome, making them potential immunogens for vaccine development. Herein we highlight literature showing that intracellular chaperone proteins GroEL and DnaK, which were originally identified as playing a role in protein folding, are relocated to the cell surface or are secreted during invasion and therefore may be recognized by the host immune system as antigens. In addition, we highlight literature showcasing the immunomodulation effects these proteins can have on the immune system, also making them potential adjuvants or immunotherapeutics.

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Could the Heat Shock Proteins 70 Family Members Exacerbate the Immune Response in Multiple Sclerosis? An in Silico Study

Cited by 20 publications

References 56 publications

A Systematic Review of Tissue and Single Cell Transcriptome/Proteome Studies of the Brain in Multiple Sclerosis

A Systematic Review of Tissue and Single Cell Transcriptome/Proteome Studies of the Brain in Multiple Sclerosis

Copper Tolerance Mechanism of the Novel Marine Multi-Stress Tolerant Yeast Meyerozyma guilliermondii GXDK6 as Revealed by Integrated Omics Analysis

Understanding GroEL and DnaK Stress Response Proteins as Antigens for Bacterial Diseases

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