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Biomedicines
Special Issues
Cellular Immune Responses in Diseases
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Cellular Immune Responses in 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 June 2024) | Viewed by 8592

Special Issue Editor

Dr. Mafalda Fonseca

E-Mail Website
Guest Editor
Health Sciences Research Centre, University of Beira Interior (CICS-UBI), 6200-506 Covilhã, Portugal
Interests: immunology; cellular immune responses; chronic diseases

Special Issue Information

Dear Colleagues,

Cellular immune responses are a crucial aspect of the immune system's defence mechanism, maintaining the right balance between protection and auto-control to avoid damaging healthy tissues or inducing chronic inflammation.

In general, these responses involve innate and adaptive mechanisms, like phagocytosis and cell-mediated cytotoxicity, engaging different leukocyte subpopulations, both antigen-specific and antigen-nonspecific cells. Antigen-specific cellular responses are orchestrated by T cells, crucial for the capacity of the organism to distinguish self from nonself. A good example is the rejection of a graft by lymphoid cells as well as graft-versus-host disease. One T cell has subpopulations of cytotoxic effector cells, which can lyse virus-infected or malignant cells. The subpopulations of helper T cells (e.g., Th1, Th2, Th17) have different patterns of effector cytokine-dependent functions after antigen recognition.

An imbalance in the cellular immune system can lead to various conditions, including autoimmune diseases, immunodeficiencies, and chronic inflammatory disorders. We expect that this Special Issue will provide fresh perspectives in the integration of knowledge concerning cellular immune responses and their regulation in disease contexts.

We invite our colleagues to submit original as well as review articles related to both non-communicable diseases/chronic diseases (e.g., neurological diseases, cardiovascular diseases, chronic respiratory diseases, chronic kidney diseases, cancer, diabetes, obesity) and communicable diseases.

Dr. Mafalda Fonseca
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • leukocyte
  • T cells
  • lymphoid cells

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Published Papers (6 papers)

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Research

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11 pages, 935 KiB  
Article
TH1 Cell Frequency and Neutrophil-to-Lymphocyte Ratio in Hemodialysis: Potential Contributions to Patient Monitoring
by Inês Rodrigues Barreto, Andreia Monteiro, Ernesto Fernandes Rocha, Catarina Reis Santos and Ana Mafalda Fonseca
Biomedicines 2024, 12(10), 2188; https://doi.org/10.3390/biomedicines12102188 - 26 Sep 2024
Viewed by 386
Abstract
Introduction: Patients undergoing hemodialysis (HD) often exhibit an impaired cellular immune response, which may contribute to an increased susceptibility to infections and other complications. Th1 cells, a subset of T-helper cells, play a crucial role in cellular immunity. However, the modulation of Th1 [...] Read more.
Introduction: Patients undergoing hemodialysis (HD) often exhibit an impaired cellular immune response, which may contribute to an increased susceptibility to infections and other complications. Th1 cells, a subset of T-helper cells, play a crucial role in cellular immunity. However, the modulation of Th1 cells by HD treatment remains unclear. Objective: This study aims to investigate the levels of circulating T cells, especially Th1 cells, and the neutrophil-to-lymphocyte ratio (NLR) in HD patients. Methods: We recruited 26 HD patients and 10 healthy volunteers. Demographical data were collected, and peripheral blood samples were analyzed. Absolute blood cell counts were determined, and T-cell populations were identified using flow cytometry. Th1 cells were defined as IFN-γ-producing CD4+ T cells after in vitro activation, and NLR was calculated through the ratio between the neutrophil and lymphocyte counts measured in peripheral blood. Results: We have observed a significant decrease in Th1 subpopulation frequency in HD patients, as well as significant correlations between immunological and demographic parameters, among which are the NLR values and the absolute values of T-cell subsets. Conclusions: These results seem to clarify the role of Th1 cells in modulating the immune responses of hemodialysis-treated patients, potentially considering its frequency as an indicator for CKD development. Full article
(This article belongs to the Special Issue Cellular Immune Responses in Diseases)
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13 pages, 2261 KiB  
Article
Comparative Evaluation of Candida Species-Specific T-Cell Immune Response in Human Peripheral Blood Mononuclear Cells
by Balaji Pathakumari, Weida Liu, Qiong Wang, Xue Kong, Guanzhao Liang, Santosh Chokkakula, Vasundhara Pathakamuri and Venkatrao Nunna
Biomedicines 2024, 12(7), 1487; https://doi.org/10.3390/biomedicines12071487 - 5 Jul 2024
Viewed by 793
Abstract
Non-albicans Candida (NAC) species are increasingly recognized as significant contributors to candidemia infections; however, relatively less is known about the immune responses induced by these species. In this study, we compared the cytokine production ability of human peripheral blood mononuclear cells (PBMCs) upon [...] Read more.
Non-albicans Candida (NAC) species are increasingly recognized as significant contributors to candidemia infections; however, relatively less is known about the immune responses induced by these species. In this study, we compared the cytokine production ability of human peripheral blood mononuclear cells (PBMCs) upon stimulation with different Candida species (Candida spp.). We measured secreted cytokines using ELISA and checked the functional profiles of T-cell responses using multicolor flow cytometry. Although there was a differential expression of cytokines against Candida spp., significant difference were observed in the levels of IFN-γ, TNF-α, IL-10, IL-12p40, and IL-23 (p < 0.05) between Candida spp. A significant difference was observed between C. albicans and C. glabrata (p = 0.026) in the levels of TNF-α. C. glabrata showed significant differences compared to C. albicans, C. parapsilosis, and C. krusei in the levels of IL-10 (p values of 0.02, 0.04, and 0.01, respectively). Despite the percentages of CD4+ and CD8+ expressing Th1, Th2, and Th17 cytokines being higher in stimulated PBMCs, none of the Candida spp. showed significant differences. The levels of secreted IL-17A and IL-23 were consistently lower in Candida spp. regardless of the stimulus used. Here, we showed the differential regulation of Th1, Th2, and Th17 during Candida spp. stimulation of the immune system ex vivo. Additionally, our findings suggest that C. albicans elicits an IFN-γ response, whereas C. glabrata promotes IL-10 cellular responses, but this warrants additional studies to conclude this association. This investigation holds the potential to advance our comprehension of the distinct immune responses induced by Candida spp., with probable implications in designing antifungal immunotherapeutics. Full article
(This article belongs to the Special Issue Cellular Immune Responses in Diseases)
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17 pages, 2254 KiB  
Article
A Novel Bionebulizer Approach to Study the Effects of Natural Mineral Water on a 3D In Vitro Nasal Model from Allergic Rhinitis Patients
by Joana Viegas, Elsa M. Cardoso, Lucile Bonneau, Ana Filipa Esteves, Catarina L. Ferreira, Gilberto Alves, António Jorge Santos-Silva, Marco Vitale, Fernando A. Arosa and Luís Taborda-Barata
Biomedicines 2024, 12(2), 408; https://doi.org/10.3390/biomedicines12020408 - 9 Feb 2024
Cited by 2 | Viewed by 1478
Abstract
Sulfurous thermal waters (STWs) are used as a complementary treatment for allergic rhinitis. However, there is scant data on the effects of STW on nasal epithelial cells, and in vitro models are warranted. The main aim of this study was to evaluate the [...] Read more.
Sulfurous thermal waters (STWs) are used as a complementary treatment for allergic rhinitis. However, there is scant data on the effects of STW on nasal epithelial cells, and in vitro models are warranted. The main aim of this study was to evaluate the dose and time effects of exposure to 3D nasal inserts (MucilAirTM-HF allergic rhinitis model) with STW or isotonic sodium chloride solution (ISCS) aerosols. Transepithelial electrical resistance (TEER) and histology were assessed before and after nebulizations. Chemokine/cytokine levels in the basal supernatants were assessed by enzyme-linked immunosorbent assay. The results showed that more than four daily nebulizations of four or more minutes compromised the normal epithelial integrity. In contrast, 1 or 2 min of STW or ISCS nebulizations had no toxic effect up to 3 days. No statistically significant changes in release of inflammatory chemokines MCP-1/CCL2 > IL-8/CXCL8 > MIP-1α/CCL3, no meaningful release of “alarmins” (IL-1α, IL-33), nor of anti-inflammatory IL-10 cytokine were observed. We have characterized safe time and dose conditions for aerosol nebulizations using a novel in vitro 3D nasal epithelium model of allergic rhinitis patients. This may be a suitable in vitro setup to mimic in vivo treatments of chronic rhinitis with STW upon triggering an inflammatory stimulus in the future. Full article
(This article belongs to the Special Issue Cellular Immune Responses in Diseases)
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15 pages, 1982 KiB  
Article
Sterile Inflammatory Response and Surgery-Related Trauma in Elderly Patients with Subtrochanteric Fractures
by Flaviu Moldovan
Biomedicines 2024, 12(2), 354; https://doi.org/10.3390/biomedicines12020354 - 2 Feb 2024
Cited by 13 | Viewed by 1336
Abstract
Sterile inflammation is a natural response of the organism in the absence of microorganisms, which is triggered in correspondence with the degree of tissue damage sustained after a surgical procedure. The objective of this study was to explore the values of postoperative hematological-derived [...] Read more.
Sterile inflammation is a natural response of the organism in the absence of microorganisms, which is triggered in correspondence with the degree of tissue damage sustained after a surgical procedure. The objective of this study was to explore the values of postoperative hematological-derived biomarkers in assessing the sterile inflammatory response magnitude related to the invasiveness of the surgical reduction technique used for subtrochanteric fractures (STFs) treatment. A retrospective, observational cohort research was conducted between January 2021 and October 2023 that included a total of 143 patients diagnosed with acute subtrochanteric fractures who underwent long Gamma Nail (LGN) fixation. According to the surgical reduction technique used, they were divided into two groups: group 1, which consisted of those with a closed reduction and internal fixation (CRIF); and group 2, which consisted of those with an open reduction internal fixation (ORIF). Between groups, statistically significant differences (p < 0.05) were found in relation to days to surgery, length of hospital stay (LOHS), duration of surgery, postoperative hemoglobin (HGB) levels, neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), monocyte–lymphocyte ratio (MLR), systemic inflammation index (SII), systemic inflammation response index (SIRI), and aggregate inflammation systemic index (AISI). The receiver operating characteristics (ROC) curve analysis revealed that all ratios presented a high diagnostic ability (p < 0.0001) with NLR > 6.95 being the most reliable (sensitivity 94.8% and specificity 70.6%). Moreover, the multivariate regression model confirmed that sterile immune response after orthopedic interventions can be assessed in an almost equal and non-dependent manner using these biomarkers. Postoperative NLR, PLR, MLR, SII, SIRI, and AISI ratios are closely correlated to the sterile inflammatory response magnitude, due to the extent of surgical dissection performed during internal fixation procedures of subtrochanteric femur fractures. Full article
(This article belongs to the Special Issue Cellular Immune Responses in Diseases)
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14 pages, 4605 KiB  
Article
Immunological Phenotyping of Mice with a Point Mutation in Cdk4
by Mehmet Yabas and Gerard F. Hoyne
Biomedicines 2023, 11(10), 2847; https://doi.org/10.3390/biomedicines11102847 - 20 Oct 2023
Viewed by 1285
Abstract
Cyclin-dependent kinases (CDKs) play a crucial role in regulation of the mammalian cell cycle. CDK4 and CDK6 control the G1/S restriction checkpoint through their ability to associate with cyclin D proteins in response to growth factor signals. CDK4 deficiency in mice gives rise [...] Read more.
Cyclin-dependent kinases (CDKs) play a crucial role in regulation of the mammalian cell cycle. CDK4 and CDK6 control the G1/S restriction checkpoint through their ability to associate with cyclin D proteins in response to growth factor signals. CDK4 deficiency in mice gives rise to a range of endocrine-specific phenotypes including diabetes, infertility, dwarfism, and atrophy of the anterior pituitary. Although CDK6 deficiency can cause thymic atrophy due to a block in the double-negative (DN) to double-positive (DP) stage of T cell development, there are no overt defects in immune cell development reported for CDK4-deficient mice. Here, we examined the impact of a novel N-ethyl-N-nitrosourea-induced point mutation in the gene encoding CDK4 on immune cell development. Mutant mice (Cdk4wnch/wnch) showed normal development and differentiation of major immune cell subsets in the thymus and spleen. Moreover, T cells from Cdk4wnch/wnch mice exhibited normal cytokine production in response to in vitro stimulation. However, analysis of the mixed bone marrow chimeras revealed that Cdk4wnch/wnch-derived T cell subsets and NK cells are at a competitive disadvantage compared to Cdk4+/+-derived cells in the thymus and periphery of recipients. These results suggest a possible role for the CDK4wnch mutation in the development of some immune cells, which only becomes apparent when the Cdk4wnch/wnch mutant cells are in direct competition with wild-type immune cells in the mixed bone marrow chimera. Full article
(This article belongs to the Special Issue Cellular Immune Responses in Diseases)
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Review

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44 pages, 2231 KiB  
Review
Urokinase-Type Plasminogen Activator Receptor (uPAR) in Inflammation and Disease: A Unique Inflammatory Pathway Activator
by Mostafa Hamada, Kyle Steven Varkoly, Omer Riyadh, Roxana Beladi, Ganesh Munuswamy-Ramanujam, Alan Rawls, Jeanne Wilson-Rawls, Hao Chen, Grant McFadden and Alexandra R. Lucas
Biomedicines 2024, 12(6), 1167; https://doi.org/10.3390/biomedicines12061167 - 24 May 2024
Cited by 1 | Viewed by 2366
Abstract
The urokinase-type plasminogen activator receptor (uPAR) is a unique protease binding receptor, now recognized as a key regulator of inflammation. Initially, uPA/uPAR was considered thrombolytic (clot-dissolving); however, recent studies have demonstrated its predominant immunomodulatory functions in inflammation and cancer. The uPA/uPAR complex has [...] Read more.
The urokinase-type plasminogen activator receptor (uPAR) is a unique protease binding receptor, now recognized as a key regulator of inflammation. Initially, uPA/uPAR was considered thrombolytic (clot-dissolving); however, recent studies have demonstrated its predominant immunomodulatory functions in inflammation and cancer. The uPA/uPAR complex has a multifaceted central role in both normal physiological and also pathological responses. uPAR is expressed as a glycophosphatidylinositol (GPI)-linked receptor interacting with vitronectin, integrins, G protein-coupled receptors, and growth factor receptors within a large lipid raft. Through protein-to-protein interactions, cell surface uPAR modulates intracellular signaling, altering cellular adhesion and migration. The uPA/uPAR also modifies extracellular activity, activating plasminogen to form plasmin, which breaks down fibrin, dissolving clots and activating matrix metalloproteinases that lyse connective tissue, allowing immune and cancer cell invasion and releasing growth factors. uPAR is now recognized as a biomarker for inflammatory diseases and cancer; uPAR and soluble uPAR fragments (suPAR) are increased in viral sepsis (COVID-19), inflammatory bowel disease, and metastasis. Here, we provide a comprehensive overview of the structure, function, and current studies examining uPAR and suPAR as diagnostic markers and therapeutic targets. Understanding uPAR is central to developing diagnostic markers and the ongoing development of antibody, small-molecule, nanogel, and virus-derived immune-modulating treatments that target uPAR. Full article
(This article belongs to the Special Issue Cellular Immune Responses in Diseases)
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