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Immunophenotyping in Autoimmune Diseases and Cancer 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (15 August 2022) | Viewed by 29196

Special Issue Editors


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Guest Editor
Biological Research Centre, Temesvári krt. 62, H-6726 Szeged, Hungary
Interests: immuno-oncology; in vitro diagnostics; single cell genomics; microarray technologies
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The mammalian immune system is a Janus-faced network of well-coordinated, highly specialized cells and biomolecules. The sensitive balance of reactive and suppressive signals maintains homeostasis in the physiological state. Under pathological conditions, however, responsiveness can escalate in autoimmune diseases or remain suppressed in cancer. In severe autoimmunity, the overwhelming immune response leads to devastating diseases, such as rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, sclerosis multiplex, etc. Conversely, immune cells, e.g., professional antigen-presenting cells and cytotoxic T cells, are not able to execute their physiological function in cancer.

Recent progress in fluorescence flow cytometry and mass cytometry has contributed to a high-dimensional resolution of the complex immunophenotype, both in autoimmune diseases and in cancer. We would like to call authors to publish their latest achievements associated with the perturbance of the regulation of immune activation and the discovery of rare subpopulations of both innate and adaptive immune players in autoimmune diseases or cancer. This Special Issue will publish works presenting not only the description of different cellular subtypes but also the identification of novel key molecular factors and biomarkers. Submission of mainly research articles is expected. Due to the recent developments in high-content, multilevel profiling technologies, review articles from pioneer scientists will also be considered.

Dr. Gabor J. Szebeni
Dr. László G. Puskás
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • immunophenotyping
  • immune regulation
  • multiparameter cytometry
  • immuno-oncology
  • anti-tumor immunity
  • autoimmunity
  • cancer immunology

Published Papers (5 papers)

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Research

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15 pages, 3706 KiB  
Article
Comparison of Homologous and Heterologous Booster SARS-CoV-2 Vaccination in Autoimmune Rheumatic and Musculoskeletal Patients
by Dániel Honfi, Nikolett Gémes, Enikő Szabó, Patrícia Neuperger, József Á. Balog, Lajos I. Nagy, Gergely Toldi, László G. Puskás, Gábor J. Szebeni and Attila Balog
Int. J. Mol. Sci. 2022, 23(19), 11411; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231911411 - 27 Sep 2022
Cited by 3 | Viewed by 2405
Abstract
Vaccination against SARS-CoV-2 to prevent COVID-19 is highly recommended for immunocompromised patients with autoimmune rheumatic and musculoskeletal diseases (aiRMDs). Little is known about the effect of booster vaccination or infection followed by previously completed two-dose vaccination in aiRMDs. We determined neutralizing anti-SARS-CoV-2 antibody [...] Read more.
Vaccination against SARS-CoV-2 to prevent COVID-19 is highly recommended for immunocompromised patients with autoimmune rheumatic and musculoskeletal diseases (aiRMDs). Little is known about the effect of booster vaccination or infection followed by previously completed two-dose vaccination in aiRMDs. We determined neutralizing anti-SARS-CoV-2 antibody levels and applied flow cytometric immunophenotyping to quantify the SARS-CoV-2 reactive B- and T-cell mediated immunity in aiRMDs receiving homologous or heterologous boosters or acquired infection following vaccination. Patients receiving a heterologous booster had a higher proportion of IgM+ SARS-CoV-2 S+ CD19+CD27+ peripheral memory B-cells in comparison to those who acquired infection. Biologic therapy decreased the number of S+CD19+; S+CD19+CD27+IgG+; and S+CD19+CD27+IgM+ B-cells. The response rate to a booster event in cellular immunity was the highest in the S-, M-, and N-reactive CD4+CD40L+ T-cell subset. Patients with a disease duration of more than 10 years had higher proportions of CD8+TNF-α+ and CD8+IFN-γ+ T-cells in comparison to patients who were diagnosed less than 10 years ago. We detected neutralizing antibodies, S+ reactive peripheral memory B-cells, and five S-, M-, and N-reactive T-cells subsets in our patient cohort showing the importance of booster events. Biologic therapy and <10 years disease duration may confound anti-SARS-CoV-2 specific immunity in aiRMDs. Full article
(This article belongs to the Special Issue Immunophenotyping in Autoimmune Diseases and Cancer 2.0)
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11 pages, 1818 KiB  
Article
MFG-E8 Reduces Aortic Intimal Proliferation in a Murine Model of Transplant Vasculopathy
by Benoit Brilland, Patrick Laplante, Pamela Thebault, Karen Geoffroy, Marie-Joëlle Brissette, Mathieu Latour, Michaël Chassé, Shijie Qi, Marie-Josée Hébert, Héloïse Cardinal and Jean-François Cailhier
Int. J. Mol. Sci. 2022, 23(8), 4094; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23084094 - 07 Apr 2022
Viewed by 1847
Abstract
Transplant vasculopathy is characterized by endothelial apoptosis, which modulates the local microenvironment. Milk fat globule epidermal growth factor 8 (MFG-E8), which is released by apoptotic endothelial cells, limits tissue damage and inflammation by promoting anti-inflammatory macrophages. We aimed to study its role in [...] Read more.
Transplant vasculopathy is characterized by endothelial apoptosis, which modulates the local microenvironment. Milk fat globule epidermal growth factor 8 (MFG-E8), which is released by apoptotic endothelial cells, limits tissue damage and inflammation by promoting anti-inflammatory macrophages. We aimed to study its role in transplant vasculopathy using the murine aortic allotransplantation model. BALB/c mice were transplanted with fully mismatched aortic transplants from MFG-E8 knockout (KO) or wild type (WT) C57BL/6J mice. Thereafter, mice received MFG-E8 (or vehicle) injections for 9 weeks prior to histopathological analysis of allografts for intimal proliferation (hematoxylin and eosin staining) and leukocyte infiltration assessment (immunofluorescence). Phenotypes of blood leukocytes and humoral responses were also evaluated (flow cytometry and ELISA). Mice receiving MFG-E8 KO aortas without MFG-E8 injections had the most severe intimal proliferation (p < 0.001). Administration of MFG-E8 decreased intimal proliferation, especially in mice receiving MFG-E8 KO aortas. Administration of MFG-E8 also increased the proportion of anti-inflammatory macrophages among graft-infiltrating macrophages (p = 0.003) and decreased systemic CD4+ and CD8+ T-cell activation (p < 0.001). An increase in regulatory T cells occurred in both groups of mice receiving WT aortas (p < 0.01). Thus, the analarmin MFG-E8 appears to be an important protein for reducing intimal proliferation in this murine model of transplant vasculopathy. MFG-E8 effects are associated with intra-allograft macrophage reprogramming and systemic T-cell activation dampening. Full article
(This article belongs to the Special Issue Immunophenotyping in Autoimmune Diseases and Cancer 2.0)
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12 pages, 2103 KiB  
Article
Reduced Expression of PD-1 in Circulating CD4+ and CD8+ Tregs Is an Early Feature of RRMS
by Maja Machcińska, Magdalena Kierasińska, Martyna Michniowska, Marta Maruszewska-Cheruiyot, Ludmiła Szewczak, Rafał Rola, Anna Karlińska, Michael Stear and Katarzyna Donskow-Łysoniewska
Int. J. Mol. Sci. 2022, 23(6), 3185; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23063185 - 16 Mar 2022
Cited by 5 | Viewed by 2175
Abstract
Altered regulatory T cell (Treg) function could contribute to MS. The expression of activating and inhibitory receptors influences the activity of Tregs. Our aim was to investigate T cell phenotypes in relapsing–remitting MS (RRMS) patients at an early phase of the disease. We [...] Read more.
Altered regulatory T cell (Treg) function could contribute to MS. The expression of activating and inhibitory receptors influences the activity of Tregs. Our aim was to investigate T cell phenotypes in relapsing–remitting MS (RRMS) patients at an early phase of the disease. We examined the influence of demographic parameters on the distribution of CD4+ and CD8+ T cell subclasses by generalized linear modeling. We also studied the expression of the following markers—CTLA-4, GITR, PD-1, FoxP3, Helios, CD28, CD62L, CD103—on T cell subsets from peripheral blood with a 14-color flow cytometry panel. We used an antibody array to define the profiles of 34 Th1/Th2/Th17 cytokines in the serum. Expression of PD-1 and GITR on CD4+ and CD8+ Tregs was decreased in RRMS patients. The proinflammatory factors IFN-γ, IL-17, IL-17F, TGFβ-1, TGFβ-3, IL-1SRII, IL-12 p40, sgp130, IL-6sR were significantly increased in RRMS patients. Therefore, a deficiency of PD-1 and GITR immune checkpoints on CD4+ and CD8+ Tregs is a feature of RRMS and might underlie impaired T cell control. Full article
(This article belongs to the Special Issue Immunophenotyping in Autoimmune Diseases and Cancer 2.0)
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13 pages, 14814 KiB  
Article
CD38 Correlates with an Immunosuppressive Treg Phenotype in Lupus-Prone Mice
by Jocelyn C. Pérez-Lara, Enrique Espinosa, Leopoldo Santos-Argumedo, Héctor Romero-Ramírez, Gabriela López-Herrera, Fabio García-García, Claudia Sandoval-Montes, Vianney Ortiz-Navarrete, Mónica Flores-Muñoz and Juan C. Rodríguez-Alba
Int. J. Mol. Sci. 2021, 22(21), 11977; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222111977 - 05 Nov 2021
Cited by 2 | Viewed by 2835
Abstract
CD38 is a transmembrane glycoprotein expressed by T-cells. It has been reported that patients with systemic lupus erythematosus (SLE) showed increased CD38+CD25+ T-cells correlating with immune activation and clinical signs. Contrariwise, CD38 deficiency in murine models has shown enhanced autoimmunity [...] Read more.
CD38 is a transmembrane glycoprotein expressed by T-cells. It has been reported that patients with systemic lupus erythematosus (SLE) showed increased CD38+CD25+ T-cells correlating with immune activation and clinical signs. Contrariwise, CD38 deficiency in murine models has shown enhanced autoimmunity development. Recent studies have suggested that CD38+ regulatory T-cells are more suppressive than CD38 regulatory T-cells. Thus, we have suggested that CD38 overexpression in SLE patients could play a role in regulating immune activation cells instead of enhancing it. This study found a correlation between CD38 with FoxP3 expression and immunosuppressive molecules (CD69, IL-10, CTLA-4, and PD-1) in T-cells from lupus-prone mice (B6.MRL-Faslpr/J). Additionally, B6.MRL-Faslpr/J mice showed a decreased proportion of CD38+ Treg cells regarding wild-type mice (WT). Furthermore, Regulatory T-Cells (Treg cells) from CD38-/- mice showed impairment in expressing immunosuppressive molecules and proliferation after stimulation through the T-cell receptor (TCR). Finally, we demonstrated an increased ratio of IFN-γ/IL-10 secretion in CD38-/- splenocytes stimulated with anti-CD3 compared with the WT. Altogether, our data suggest that CD38 represents an element in maintaining activated and proliferative Treg cells. Consequently, CD38 could have a crucial role in immune tolerance, preventing SLE development through Treg cells. Full article
(This article belongs to the Special Issue Immunophenotyping in Autoimmune Diseases and Cancer 2.0)
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Review

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23 pages, 893 KiB  
Review
Nutritional Management of Thyroiditis of Hashimoto
by Yana Danailova, Tsvetelina Velikova, Georgi Nikolaev, Zorka Mitova, Alexander Shinkov, Hristo Gagov and Rossitza Konakchieva
Int. J. Mol. Sci. 2022, 23(9), 5144; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23095144 - 05 May 2022
Cited by 16 | Viewed by 19048
Abstract
Since the thyroid gland is one of the organs most affected by autoimmune processes, many patients with thyroiditis of Hashimoto (TH) seek medical advice on lifestyle variance and dietary modifications to improve and maintain their hyroid function. In this review, we aim to [...] Read more.
Since the thyroid gland is one of the organs most affected by autoimmune processes, many patients with thyroiditis of Hashimoto (TH) seek medical advice on lifestyle variance and dietary modifications to improve and maintain their hyroid function. In this review, we aim to present and discuss some challenges associated with the nutritional management of TH, focusing on environmental and dietary deficits, inflammatory and toxic nutrients, cyanotoxins, etc. We discuss the relationships among different diets, chronic inflammation, and microbiota, and their impact on the development and exacerbation of TH in detail. We share some novel insights into the role of vitamin D and melatonin for preserving thyroid function during chronic inflammation in autoimmune predisposed subjects. A comprehensive overview is provided on anti-inflammatory nutrients and ecological diets, including foods for cleansing and detoxification, which represent strategies to prevent relapses and achieve overall improvement of life quality. In conclusion, data from biomedical and clinical studies provide evidence that an appropriate dietary and lighting regimen could significantly improve the function of the thyroid gland and reduce the reactivity of autoantibodies in TH. Compliance with nutritional guidelines may help TH patients to reduce the need for medicines. Full article
(This article belongs to the Special Issue Immunophenotyping in Autoimmune Diseases and Cancer 2.0)
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