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The Role of T Cells in Immunomodulation: Focus on Molecular Mechanisms

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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: 30 August 2024 | Viewed by 4330

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Dr. Katarzyna A. Lisowska

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Guest Editor

Department of Physiopathology, Faculty of Medicine, Medical University of Gdańsk, 80-210 Gdańsk, Poland
Interests: T cells; B cells; inflammation; immunomodulation; autoimmune diseases; kidney diseases; depression

Special Issue Information

Dear Colleagues,

Immunomodulation is the process of stimulating the immune system with various substances in order to influence immune responses. In practice, this usually means an action aimed at increasing the immune system's activity, which helps fight infections or cancer cells. Immunomodulators could also be used to reduce undesirable inflammatory responses, which lead to hypersensitivity reactions. For this reason, broadly understood, immunomodulation plays a significant role in treating cancer, autoimmune diseases, and immunodeficiencies. The methods of immunomodulation are very diverse, and one of its goals is to modify the response of T cells. A balance between engagement of activating and inhibitory receptors influences the outcome of T cell activation. In recent years, there have been considerable advances in our knowledge of the cellular and molecular events which control T cell activity. This Special Issue is dedicated to all important advances in the molecular mechanisms of immunomodulation mediated by T cells.

Dr. Katarzyna A. Lisowska
Guest Editor

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Keywords

helper T cells
regulatory T cells
cytotoxic T cells
activating receptors
inhibitory receptors
immunomodulation

Published Papers (4 papers)

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Research

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15 pages, 8970 KiB

Open AccessArticle

Trichinella spiralis Paramyosin Alleviates Collagen-Induced Arthritis in Mice by Modulating CD4⁺ T Cell Differentiation

by Dongwan Zhang, Wang Jiang, Yan Yu, Jingjing Huang, Zhihui Jia, Yuli Cheng and Xinping Zhu

Int. J. Mol. Sci. 2024, 25(12), 6706; https://doi.org/10.3390/ijms25126706 - 18 Jun 2024

Viewed by 451

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease that significantly impacts quality of life by disrupting CD4⁺ T cell immune homeostasis. The identification of a low-side-effect drug for RA treatment is urgently needed. Our previous study suggests that Trichinella spiralis paramyosin (Ts-Pmy) has immunomodulatory effects, but its potential effect on CD4⁺ T cell response in RA remains unclear. In this study, we used a murine model to investigate the role of rTs-Pmy in regulating CD4⁺ T cell differentiation in collagen-induced arthritis (CIA). Additionally, we assessed the impact of rTs-Pmy on CD4⁺ T cell differentiation towards the Th1 and Th17 phenotypes, which are associated with inflammatory responses in arthritis, using in vitro assays. The results demonstrated that rTs-Pmy administration reduced arthritis severity by inhibiting Th1 and Th17 response while enhancing Treg response. Prophylactic administration of Ts-Pmy showed superior efficacy on CIA compared to therapeutic administration. Furthermore, in vitro assays demonstrated that rTs-Pmy could inhibit the differentiation of CD4⁺ T cells into Th1 and Th17 while inducing the production of Tregs, suggesting a potential mechanism underlying its therapeutic effects. This study suggests that Ts-Pmy may ameliorate CIA by restoring the immune balance of CD4⁺ T cells and provides new insights into the mechanism through which helminth-derived proteins exert their effects on autoimmune diseases. Full article

(This article belongs to the Special Issue The Role of T Cells in Immunomodulation: Focus on Molecular Mechanisms)

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17 pages, 2368 KiB

Open AccessArticle

Differential Impact of CD43 and CD28 on T-Cell Differentiation Depending on the Order of Engagement with the TCR

by Monserrat Alba Sandoval-Hernández, Nora Alma Fierro, José Ignacio Veytia-Bucheli, Den Alejandro Alvarado-Velázquez, Estefanía Alemán-Navarro, Erika Melchy-Pérez, Constance Auvynet, Iván Imaz-Rosshandler, Jorge Carneiro, Ernesto Perez-Rueda and Yvonne Rosenstein

Int. J. Mol. Sci. 2024, 25(6), 3135; https://doi.org/10.3390/ijms25063135 - 8 Mar 2024

Viewed by 1338

Abstract

The combination of signals from the T-cell receptor (TCR) and co-stimulatory molecules triggers transcriptional programs that lead to proliferation, cytokine secretion, and effector functions. We compared the impact of engaging the TCR with CD28 and/or CD43 at different time points relative to TCR engagement on T-cell function. TCR and CD43 simultaneous engagement resulted in higher CD69 and PD-1 expression levels than in TCR and CD28-stimulated cells, with a cytokine signature of mostly effector, inflammatory, and regulatory cytokines, while TCR and CD28-activated cells secreted all categories of cytokines, including stimulatory cytokines. Furthermore, the timing of CD43 engagement relative to TCR ligation, and to a lesser degree that of CD28, resulted in distinct patterns of expression of cytokines, chemokines, and growth factors. Complete cell activation was observed when CD28 or CD43 were engaged simultaneously with or before the TCR, but ligating the TCR before CD43 or CD28 failed to complete a cell activation program regarding cytokine secretion. As the order in which CD43 or CD28 and the TCR were engaged resulted in different combinations of cytokines that shape distinct T-cell immune programs, we analyzed their upstream sequences to assess whether the combinations of cytokines were associated with different sets of regulatory elements. We found that the order in which the TCR and CD28 or CD43 are engaged predicts the recruitment of specific sets of chromatin remodelers and TFSS, which ultimately regulate T-cell polarization and plasticity. Our data underscore that the combination of co-stimulatory molecules and the time when they are engaged relative to the TCR can change the cell differentiation program. Full article

(This article belongs to the Special Issue The Role of T Cells in Immunomodulation: Focus on Molecular Mechanisms)

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Review

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27 pages, 2066 KiB

Open AccessReview

Complex Role of Regulatory T Cells (Tregs) in the Tumor Microenvironment: Their Molecular Mechanisms and Bidirectional Effects on Cancer Progression

by Yu Wang, Jiazhou Li, Shingo Nakahata and Hidekatsu Iha

Int. J. Mol. Sci. 2024, 25(13), 7346; https://doi.org/10.3390/ijms25137346 - 4 Jul 2024

Viewed by 384

Abstract

Regulatory T cells (Tregs) possess unique immunosuppressive activity among CD4-positive T cells. Tregs are ubiquitously present in mammals and function to calm excessive immune responses, thereby suppressing allergies or autoimmune diseases. On the other hand, due to their immunosuppressive function, Tregs are thought to promote cancer progression. The tumor microenvironment (TME) is a multicellular system composed of many cell types, including tumor cells, infiltrating immune cells, and cancer-associated fibroblasts (CAFs). Within this environment, Tregs are recruited by chemokines and metabolic factors and impede effective anti-tumor responses. However, in some cases, their presence can also improve patient’s survival rates. Their functional consequences may vary across tumor types, locations, and stages. An in-depth understanding of the precise roles and mechanisms of actions of Treg is crucial for developing effective treatments, emphasizing the need for further investigation and validation. This review aims to provide a comprehensive overview of the complex and multifaceted roles of Tregs within the TME, elucidating cellular communications, signaling pathways, and their impacts on tumor progression and highlighting their potential anti-tumor mechanisms through interactions with functional molecules. Full article

(This article belongs to the Special Issue The Role of T Cells in Immunomodulation: Focus on Molecular Mechanisms)

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14 pages, 837 KiB

Open AccessReview

The Role of the CD28 Family Receptors in T-Cell Immunomodulation

by Klaudia Ciesielska-Figlon and Katarzyna A. Lisowska

Int. J. Mol. Sci. 2024, 25(2), 1274; https://doi.org/10.3390/ijms25021274 - 20 Jan 2024

Cited by 1 | Viewed by 1513

Abstract

The CD28 family receptors include the CD28, ICOS (inducible co-stimulator), CTLA-4 (cytotoxic T-lymphocyte antigen-4), PD-1 (programmed cell death protein 1), and BTLA (B- and T-lymphocyte attenuator) molecules. They characterize a group of molecules similar to immunoglobulins that control the immune response through modulating T-cell activity. Among the family members, CD28 and ICOS act as enhancers of T-cell activity, while three others—BTLA, CTLA-4, and PD-1—function as suppressors. The receptors of the CD28 family interact with the B7 family of ligands. The cooperation between these molecules is essential for controlling the course of the adaptive response, but it also significantly impacts the development of immune-related diseases. This review introduces the reader to the molecular basis of the functioning of CD28 family receptors and their impact on T-cell activity. Full article

(This article belongs to the Special Issue The Role of T Cells in Immunomodulation: Focus on Molecular Mechanisms)

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The Role of T Cells in Immunomodulation: Focus on Molecular Mechanisms

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