Advances in Cellular and Molecular Treatment of Autoimmune Diseases

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Immunology".

Deadline for manuscript submissions: 30 September 2024 | Viewed by 10048

Special Issue Editors


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Guest Editor
Department of Rheumatology, St. Paul’s Hospital, Thessaloniki, Greece
Interests: rheumatoid arthritis; tumour necrosis factor; fatty acids; treatment
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Department of Internal Medicine and Autoimmune Rheumatic Diseases, School of Medicine, University of Thessaly, Larissa, Greece
Interests: autoimmunity; autoimmune diseases; diet; immunosupression; immunoregulation; microbiome; nutrition; rheumatic diseases
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Asclepeion Hospital, Athens, Greece
Interests: rheumatoid arthritis; diabetes mellitus; oncology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Lately, there is a world-wide increase in the prevalence and incidence of autoimmune diseases. Hence, extensive research is performed in order the identify causes and risk factors of autoimmune diseases. Extensive research in the pathophysiology of autoimmune diseases has revealed the implication of various factors in their pathogenesis. Treatment of autoimmune diseases has been the subject of fruitful research in recent years. Corticosteroids may be applied as early treatment. Disease modifying non-biologic drugs such as methotrexate, leflunomide, sulfasalazine and hydroxychloroquine have been used and may alter disease prognosis. Biologic agents targeting cellular and molecular targets have been introduced in the treatment of autoimmune diseases and have induced disease remission and may have altered disease progression and long-term disease prognosis. Biologic agents may be used either intravenously or subcutaneously. However, biologic agents are related with a high cost. Therefore, biosimilars of these agents have been introduced in the treatment of autoimmune diseases. The concurrent application of non-biologic disease modifying agents and biologics is discussed. Currently, there is availability of diverse effective agents targeting cellular and molecular targets in the treatment of autoimmune diseases and has enabled the modification of treatment regimens to the needs of each individual patient.

Dr. Panagiotis Athanassiou
Prof. Dr. Dimitrios P. Bogdanos
Dr. Ifigenia Kostoglou-Athanassiou
Guest Editors

Manuscript Submission Information

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Keywords

  • autoimmune diseases
  • disease activity
  • TNFa inhibitors
  • tocilizumab
  • infliximab
  • golimumab
  • etanercept
  • JAK inhibitors
  • cellular targets
  • molecular targets

Published Papers (4 papers)

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Research

15 pages, 2385 KiB  
Article
People with Primary Progressive Multiple Sclerosis Have a Lower Number of Central Memory T Cells and HLA-DR+ Tregs
by João Canto-Gomes, Sara Da Silva-Ferreira, Carolina S. Silva, Daniela Boleixa, Ana Martins da Silva, Inés González-Suárez, João J. Cerqueira, Margarida Correia-Neves and Claudia Nobrega
Cells 2023, 12(3), 439; https://doi.org/10.3390/cells12030439 - 29 Jan 2023
Cited by 5 | Viewed by 2239
Abstract
The importance of circulating immune cells to primary progressive multiple sclerosis (PPMS) pathophysiology is still controversial because most immunotherapies were shown to be ineffective in treating people with PPMS (pwPPMS). Yet, although controversial, data exist describing peripheral immune system alterations in pwPPMS. This [...] Read more.
The importance of circulating immune cells to primary progressive multiple sclerosis (PPMS) pathophysiology is still controversial because most immunotherapies were shown to be ineffective in treating people with PPMS (pwPPMS). Yet, although controversial, data exist describing peripheral immune system alterations in pwPPMS. This study aims to investigate which alterations might be present in pwPPMS free of disease-modifying drugs (DMD) in comparison to age- and sex-matched healthy controls. A multicentric cross-sectional study was performed using 23 pwPPMS and 23 healthy controls. The phenotype of conventional CD4+ and CD8+ T cells, regulatory T cells (Tregs), B cells, natural killer (NK) T cells and NK cells was assessed. Lower numbers of central memory CD4+ and CD8+ T cells and activated HLA-DR+ Tregs were observed in pwPPMS. Regarding NK and NKT cells, pwPPMS presented higher percentages of CD56dimCD57+ NK cells expressing NKp46 and of NKT cells expressing KIR2DL2/3 and NKp30. Higher disease severity scores and an increasing time since diagnosis was correlated with lower numbers of inhibitory NK cells subsets. Our findings contribute to reinforcing the hypotheses that alterations in peripheral immune cells are present in pwPPMS and that changes in NK cell populations are the strongest correlate of disease severity. Full article
(This article belongs to the Special Issue Advances in Cellular and Molecular Treatment of Autoimmune Diseases)
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26 pages, 4620 KiB  
Article
The Potential Role of Cytotoxic Immune Effectors in Induction, Progression and Pathogenesis of Amyotrophic Lateral Sclerosis (ALS)
by Kawaljit Kaur, Po-Chun Chen, Meng-Wei Ko, Ao Mei, Nishant Chovatiya, Sara Huerta-Yepez, Weiming Ni, Sean Mackay, Jing Zhou, Dipanarine Maharaj, Subramaniam Malarkannan and Anahid Jewett
Cells 2022, 11(21), 3431; https://doi.org/10.3390/cells11213431 - 31 Oct 2022
Cited by 12 | Viewed by 2542
Abstract
Amyotrophic lateral sclerosis (ALS) is an auto-immune neurodegenerative disorder affecting the motor-neuron system. The causes of ALS are heterogeneous, and are only partially understood. We studied different aspects of immune pathogenesis in ALS and found several basic mechanisms which are potentially involved in [...] Read more.
Amyotrophic lateral sclerosis (ALS) is an auto-immune neurodegenerative disorder affecting the motor-neuron system. The causes of ALS are heterogeneous, and are only partially understood. We studied different aspects of immune pathogenesis in ALS and found several basic mechanisms which are potentially involved in the disease. Our findings demonstrated that ALS patients’ peripheral blood contains higher proportions of NK and B cells in comparison to healthy individuals. Significantly increased IFN-γ secretion by anti-CD3/28 mAbs-treated peripheral blood mononuclear cells (PBMCs) were observed in ALS patients, suggesting that hyper-responsiveness of T cell compartment could be a potential mechanism for ALS progression. In addition, elevated granzyme B and perforin secretion at a single cell level, and increased cytotoxicity and secretion of IFN-γ by patients’ NK cells under specific treatment conditions were also observed. Increased IFN-γ secretion by ALS patients’ CD8+ T cells in the absence of IFN-γ receptor expression, and increased CD8+ T cell effector/memory phenotype as well as increased granzyme B at the single cell level points to the CD8+ T cells as potential cells in targeting motor neurons. Along with the hyper-responsiveness of cytotoxic immune cells, significantly higher levels of inflammatory cytokines including IFN-γ was observed in peripheral blood-derived serum of ALS patients. Supernatants obtained from ALS patients’ CD8+ T cells induced augmented cell death and differentiation of the epithelial cells. Weekly N-acetyl cysteine (NAC) infusion in patients decreased the levels of many inflammatory cytokines in peripheral blood of ALS patient except IFN-γ, TNF-α, IL-17a and GMCSF which remained elevated. Findings of this study indicated that CD8+ T cells and NK cells are likely culprits in targeting motor neurons and therefore, strategies should be designed to decrease their function, and eliminate the aggressive nature of these cells. Analysis of genetic mutations in ALS patient in comparison to identical twin revealed a number of differences and similarities which may be important in the pathogenesis of the disease. Full article
(This article belongs to the Special Issue Advances in Cellular and Molecular Treatment of Autoimmune Diseases)
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15 pages, 6199 KiB  
Article
Synovial Macrophages Expression of OX40L Is Required for Follicular Helper T Cells Differentiation in the Joint Microenvironment
by Xiaoyu Cai, Meng Zhang, Fujia Ren, Weidong Fei, Xiao Zhang, Yunchun Zhao, Yao Yao and Nengming Lin
Cells 2022, 11(20), 3326; https://doi.org/10.3390/cells11203326 - 21 Oct 2022
Cited by 4 | Viewed by 1630
Abstract
Signaling via the OX40/OX40L axis plays a key role in CD4+ T cell development, and OX40L expression is primarily restricted to antigen-presenting cells (APCs). This study was designed to assess the role of APC-mediated OX40L expression in the context of the development [...] Read more.
Signaling via the OX40/OX40L axis plays a key role in CD4+ T cell development, and OX40L expression is primarily restricted to antigen-presenting cells (APCs). This study was designed to assess the role of APC-mediated OX40L expression in the context of the development of rheumatoid arthritis (RA)-associated CD4+ T cell subsets. For these analyses, clinical samples were harvested from patients with osteoarthritis and RA, with additional analyses performed using OX40−/− mice and mice harboring monocyte/macrophage-specific deletions of OX40L. Together, these analyses revealed tissue-specific roles for OX40/OX40L signaling in RA. Specifically, higher levels of synovial macrophage OX40L expression were associated with the enhanced development of T follicular helper cells in the joint microenvironment, thereby contributing to the pathogenesis of RA. This Tfh differentiation was found to be OX40/OX40L-dependent in this synovial setting. Overall, these results indicate that the expression of OX40L by synovia macrophages is necessary to support Tfh differentiation in the joint tissues, thus offering new insight regarding the etiological basis for RA progression. Full article
(This article belongs to the Special Issue Advances in Cellular and Molecular Treatment of Autoimmune Diseases)
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19 pages, 6355 KiB  
Article
Characterization of Peripheral Blood TCR in Patients with Type 1 Diabetes Mellitus by BD RhapsodyTM VDJ CDR3 Assay
by Takuro Okamura, Masahide Hamaguchi, Hiroyuki Tominaga, Noriyuki Kitagawa, Yoshitaka Hashimoto, Saori Majima, Takafumi Senmaru, Hiroshi Okada, Emi Ushigome, Naoko Nakanishi, Shigeyuki Shichino and Michiaki Fukui
Cells 2022, 11(10), 1623; https://doi.org/10.3390/cells11101623 - 12 May 2022
Cited by 1 | Viewed by 2855
Abstract
The sequence of complementarity-determining region 3 of the T-cell receptor (TCR) varies widely due to the insertion of random bases during V-(D)-J recombination. In this study, we used single-cell VDJ sequencing using the latest technology, BD Rhapsody, to identify the TCR sequences of [...] Read more.
The sequence of complementarity-determining region 3 of the T-cell receptor (TCR) varies widely due to the insertion of random bases during V-(D)-J recombination. In this study, we used single-cell VDJ sequencing using the latest technology, BD Rhapsody, to identify the TCR sequences of autoreactive T-cells characteristic of Japanese type 1 diabetes mellitus (T1DM) and to clarify the pairing of TCR of peripheral blood mononuclear cells from four patients with T1DM at the single-cell level. The expression levels of the TCR alpha variable (TRAV) 17 and TRAV21 in T1DM patients were higher than those in healthy Japanese subjects. Furthermore, the Shannon index of CD8+ T cells and FOXP3+ cells in T1DM patients was lower than that of healthy subjects. The gene expression of PRF1, GZMH, ITGB2, NKG7, CTSW, and CST7 was increased, while the expression of CD4, CD7, CD5, HLA-A, CD27, and IL-32 was decreased in the CD8+ T cells of T1DM patients. The upregulated gene expression was IL4R and TNFRSF4 in FOXP3+ cells of T1DM patients. Overall, these findings demonstrate that TCR diversity and gene expression of CD8+ and FOXP3+ cells are different in patients with T1DM and healthy subjects. Full article
(This article belongs to the Special Issue Advances in Cellular and Molecular Treatment of Autoimmune Diseases)
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