Immune Cell Profiling in Human Diseases

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (30 April 2023) | Viewed by 9798

Special Issue Editors

Department of Biological Sciences and Biotechnology, Chungbuk National University, Cheongju 28644, Korea
Interests: immunology; macrophages; interferon; tumor-associated macrophages

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Guest Editor
School of Life Sciences, Ulsan National Institute of Science & Technology (UNIST), Ulsan 44919, Republic of Korea
Interests: COVID-19; SARS-CoV-2; inflammatory cytokines; innate immune response; macrophage

Special Issue Information

Dear Colleagues,

Abnormal immune cells play a crucial role in the pathogenesis and exacerbation of various human diseases including many cancers and autoimmune diseases. Therefore, profiling of immune cells specifically present in a certain disease microenvironment can provide critical clues for the diagnosis and treatment of diseases. In the past decade, with the development of next-generation sequencing technology, immune cell profiling has being carried out across a variety of diseased tissues. Transcriptomic analysis of immune cells using RNA-seq provides differential gene regulation by various stimuli from the disease environment. Using epigenomic techniques such as ATAC-seq and ChIP-seq, it is possible to find key transcription factors and cis-regulatory elements that control gene expression in human diseases. In addition, through metabolomics, some metabolites in the disease environment contribute to epigenetic and transcriptomic changes. Recent investigations have been shown that immune profiling of human diseases at the multi-omics level reveals the composition and heterogeneity of specific immune cells within tissues in human diseases. The application of omics technology at the single-cell level sheds light on the more precise immune profiling in human diseases. In this Special Issue, we would like to collect recent publications on the research results and knowledge related to immune profiling using omics technology in various human diseases.

Dr. Kyuho Kang
Dr. Sungho Park
Guest Editors

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Keywords

  • immune profiling
  • macrophages
  • cancers
  • autoimmune diseases
  • transcriptomics
  • epigenomics
  • metabolomics
  • scRNA-seq
  • scATAC-seq

Published Papers (4 papers)

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Research

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14 pages, 3033 KiB  
Article
The Abundance of Tumor-Infiltrating CD8+ Tissue Resident Memory T Lymphocytes Correlates with Patient Survival in Glioblastoma
by Marco Pio La Manna, Diana Di Liberto, Marianna Lo Pizzo, Leila Mohammadnezhad, Mojtaba Shekarkar Azgomi, Vincenzo Salamone, Valeria Cancila, Davide Vacca, Costanza Dieli, Rosario Maugeri, Lara Brunasso, Domenico Gerardo Iacopino, Francesco Dieli and Nadia Caccamo
Biomedicines 2022, 10(10), 2454; https://doi.org/10.3390/biomedicines10102454 - 1 Oct 2022
Cited by 2 | Viewed by 2109
Abstract
Glial tumors alone account for 40% of all CNS tumors and present a low survival rate. The tumor microenvironment is a critical regulator of tumor progression and therapeutic effectiveness in glioma. Growing evidence from numerous studies of human solid tumor-infiltrating CD8+ T [...] Read more.
Glial tumors alone account for 40% of all CNS tumors and present a low survival rate. The tumor microenvironment is a critical regulator of tumor progression and therapeutic effectiveness in glioma. Growing evidence from numerous studies of human solid tumor-infiltrating CD8+ T cells indicates that tissue-resident memory T cells (TRM) represent a substantial subpopulation of tumor-infiltrating lymphocytes (TILs). Although it is reported that some types of cancer patients with high immune infiltration tend to have better outcomes than patients with low immune infiltration, it seems this does not happen in gliomas. This study aimed to characterize TRMs cells in the glioma tumor microenvironment to identify their potential predictive and prognostic role and the possible therapeutic applications. Fluorescence activated cell sorting (FACS) analysis and immunofluorescence staining highlighted a statistically significant increase in CD8+ TRM cells (CD103+ and CD69+ CD8+ T cells) in gliomas compared to control samples (meningioma). In-silico analysis of a dataset of n = 153 stage IV glioma patients confirmed our data. Moreover, the gene expression analysis showed an increase in the expression of TRM-related genes in tumor tissues compared to normal tissues. This analysis also highlighted the positive correlation between genes associated with CD8+ TRM and TILs, indicating that CD8+ TRMs cells are present among the infiltrating T cells. Finally, high expression of Integrin subunit alpha E (ITGAE), the gene coding for the integrin CD103, and high CD8+ TILs abundance were associated with more prolonged survival, whereas high ITGAE expression but low CD8+ TILs abundance were associated with lower survival. Full article
(This article belongs to the Special Issue Immune Cell Profiling in Human Diseases)
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18 pages, 4061 KiB  
Article
Effects of Human RelA Transgene on Murine Macrophage Inflammatory Responses
by Stamatia Papoutsopoulou, Lorna Morris, Andrew Bayliff, Thomas Mair, Hazel England, Massimiliano Stagi, François Bergey, Mohammad Tauqeer Alam, Raheleh Sheibani-Tezerji, Philip Rosenstiel, Werner Müller, Vitor A. P. Martins Dos Santos and Barry J. Campbell
Biomedicines 2022, 10(4), 757; https://doi.org/10.3390/biomedicines10040757 - 24 Mar 2022
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Abstract
The NFκB transcription factors are major regulators of innate immune responses, and NFκB signal pathway dysregulation is linked to inflammatory disease. Here, we utilised bone marrow-derived macrophages from the p65-DsRedxp/IκBα-eGFP transgenic strain to study the functional implication of xenogeneic (human) RelA(p65) protein introduced [...] Read more.
The NFκB transcription factors are major regulators of innate immune responses, and NFκB signal pathway dysregulation is linked to inflammatory disease. Here, we utilised bone marrow-derived macrophages from the p65-DsRedxp/IκBα-eGFP transgenic strain to study the functional implication of xenogeneic (human) RelA(p65) protein introduced into the mouse genome. Confocal imaging showed that human RelA is expressed in the cells and can translocate to the nucleus following activation of Toll-like receptor 4. RNA sequencing of lipid A-stimulated macrophages, revealed that human RelA impacts on murine gene transcription, affecting both non-NFκB and NFκB target genes, including immediate-early and late response genes, e.g., Fos and Cxcl10. Validation experiments on NFκB targets revealed markedly reduced mRNA levels, but similar kinetic profiles in transgenic cells compared to wild-type. Enrichment pathway analysis of differentially expressed genes revealed interferon and cytokine signaling were affected. These immune response pathways were also affected in macrophages treated with tumor necrosis factor. Data suggests that the presence of xenogeneic RelA protein likely has inhibitory activity, altering specific transcriptional profiles of key molecules involved in immune responses. It is therefore essential that this information be taken into consideration when designing and interpreting future experiments using this transgenic strain. Full article
(This article belongs to the Special Issue Immune Cell Profiling in Human Diseases)
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15 pages, 1776 KiB  
Article
Influence of Fetomaternal Microchimerism on Maternal NK Cell Reactivity against the Child’s Leukemic Blasts
by Lena-Marie Martin, Anne Kruchen, Boris Fehse and Ingo Müller
Biomedicines 2022, 10(3), 603; https://doi.org/10.3390/biomedicines10030603 - 4 Mar 2022
Cited by 1 | Viewed by 2422
Abstract
Persistence of fetal cells in the circulation of the mother (fetal microchimerism, FM) is associated with increased survival and reduced relapse of children with leukemia receiving a haploidentical hematopoietic stem cell transplantation (hHSCT). NK cells play an important role in maternal tolerance towards [...] Read more.
Persistence of fetal cells in the circulation of the mother (fetal microchimerism, FM) is associated with increased survival and reduced relapse of children with leukemia receiving a haploidentical hematopoietic stem cell transplantation (hHSCT). NK cells play an important role in maternal tolerance towards the unborn child. In this study, 70 mother–child pairs were prospectively analyzed for the occurrence of FM, KIR genotype and HLA-C type. We found that occurrence and level of FM were influenced by three maternal genetic factors: presence of an HLA-C1 allele, absence of KIR2DL3 and presence of a cen-B/B motif. Furthermore, an HLA-C match between mother and child favored persistence of FM. NK cells from FM+ mothers showed a 40% higher specific degranulation against their filial leukemic blasts than NK cells from FM mothers, suggesting the presence of educated maternal NK cells. Nevertheless, cytotoxicity of parental NK cells against filial leukemic blasts was independent of KIR genetics (haplotype, B content score, centromeric and telomeric KIR gene regions) and independent of FM, indicating that additional immune effector mechanisms contribute to the beneficial effect of persisting FM in hHSCT. Full article
(This article belongs to the Special Issue Immune Cell Profiling in Human Diseases)
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Review

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18 pages, 336 KiB  
Review
Immunosenescence in Neurological Diseases—Is There Enough Evidence?
by Paulus S Rommer, Gabriel Bsteh, Tobias Zrzavy, Romana Hoeftberger and Thomas Berger
Biomedicines 2022, 10(11), 2864; https://doi.org/10.3390/biomedicines10112864 - 9 Nov 2022
Cited by 4 | Viewed by 1873
Abstract
The aging of the immune system has recently attracted a lot of attention. Immune senescence describes changes that the immune system undergoes over time. The importance of immune senescence in neurological diseases is increasingly discussed. For this review, we considered studies that investigated [...] Read more.
The aging of the immune system has recently attracted a lot of attention. Immune senescence describes changes that the immune system undergoes over time. The importance of immune senescence in neurological diseases is increasingly discussed. For this review, we considered studies that investigated cellular changes in the aging immune system and in neurological disease. Twenty-six studies were included in our analysis (for the following diseases: multiple sclerosis, stroke, Parkinson’s disease, and dementia). The studies differed considerably in terms of the patient groups included and the cell types studied. Evidence for immunosenescence in neurological diseases is currently very limited. Prospective studies in well-defined patient groups with appropriate control groups, as well as comprehensive methodology and reporting, are essential prerequisites to generate clear insights into immunosenescence in neurological diseases. Full article
(This article belongs to the Special Issue Immune Cell Profiling in Human Diseases)
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