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Special Issue "The Role of Interleukin in Health and Diseases"

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

Deadline for manuscript submissions: 30 November 2021.

Special Issue Editor

Dr. Yuji Takeda
E-Mail Website1 Website2
Guest Editor
Department of Immunology, Yamagata University Faculty of Medicine, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan
Interests: biodefence; cancer immunity; cytokine; diversity of myeloid cell; diversity of cell signaling; immunology; inflammatory disease; innate immunity; myeloid-derived suppressor cell (MDSC); neutrophils

Special Issue Information

Dear Colleagues,

Interleukin is a general term for physiologically active substances produced by various cells including immune cells. Most interleukins are glycoproteins, the molecular weight of which is around 10,000 to 100,000. One interleukin molecule exerts various physiological activities. Interestingly, a cascade network of interleukin production exists with its inhibitor production. Therefore, interleukins are essential for cells to interact with each other, and are also called "words" used by cells. Words (interleukins) harmonize the innate immune system and the acquired immune system, and then defend from infection.

Recently, autoimmune diseases, cancer (carcinogenesis/angiogenesis/metastasis), neurodegenerative diseases, arteriosclerotic diseases, and COVID-19 cytokine storm have been added to the definition of words classified as inflammatory cytokines. To read these words, studies on interleukin production mechanisms, gene regulation mechanisms, receptor systems, and signal transduction have been vigorously conducted, and the meaning of words has become clearer. Furthermore, words are released not only from immune cells but also from various tissues such as fat, muscle, and nerve. By reading words from various tissues, it is possible to understand the homeostatic breakdown in a body.

At present, we are able to read some of the words and to assume the behavior of cells. By overwriting cell words with anti-TNFα antibody, anti-IL-6 receptor antibody, IL-1ra, and JAK inhibitor, it has become possible to suppress the behavior of inflammatory cells. However, we have not yet fully understood the complex conversations created by cell interactions. In the future, understanding the network structure of words as conversation will open a new avenue to develop therapies for various diseases.

The Special Issue "Interleukin" covers the actions of interleukins in various diseases, production mechanisms, gene regulation mechanisms, receptor systems, signal transduction, and systems biological approaches. We hope that this Special Issue will provide a platform for enhancing research on interleukins.

Dr. Yuji Takeda
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 papers will be 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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • interleukins in physiology
  • receptor system
  • signal transduction
  • gene regulation
  • interleukins in pathology
  • inflammation
  • autoimmune disease
  • inhibitor of interleukins
  • network of interleukins

Published Papers (6 papers)

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Research

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Article
Oral Squamous Cell Carcinoma Contributes to Differentiation of Monocyte-Derived Tumor-Associated Macrophages via PAI-1 and IL-8 Production
Int. J. Mol. Sci. 2021, 22(17), 9475; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22179475 - 31 Aug 2021
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Abstract
Tumor-associated macrophages (TAMs) promote cancer cell proliferation and metastasis, as well as anti-tumor immune suppression. Recent studies have shown that tumors enhance the recruitment and differentiation of TAMs, but the detailed mechanisms have not been clarified. We thus examined the influence of cancer [...] Read more.
Tumor-associated macrophages (TAMs) promote cancer cell proliferation and metastasis, as well as anti-tumor immune suppression. Recent studies have shown that tumors enhance the recruitment and differentiation of TAMs, but the detailed mechanisms have not been clarified. We thus examined the influence of cancer cells on the differentiation of monocytes to TAM subsets, including CD163+, CD204+, and CD206+ cells, in oral squamous cell carcinoma (OSCC) using immunohistochemistry, flow cytometry, and a cytokine array. Furthermore, we investigated the effect of OSCC cells (HSC-2, SQUU-A, and SQUU-B cells) on the differentiation of purified CD14+ cells to TAM subsets. The localization patterns of CD163+, CD204+, and CD206+ in OSCC sections were quite different. The expression of CD206 on CD14+ cells was significantly increased after the co-culture with OSCC cell lines, while the expressions of CD163 and CD204 on CD14+ cells showed no change. High concentrations of plasminogen activator inhibitor-1 (PAI-1) and interleukin-8 (IL-8) were detected in the conditioned medium of OSCC cell lines. PAI-1 and IL-8 stimulated CD14+ cells to express CD206. Moreover, there were positive correlations among the numbers of CD206+, PAI-1+, and IL-8+ cells in OSCC sections. These results suggest that PAI-1 and IL-8 produced by OSCC contribute to the differentiation of monocytes to CD206+ TAMs. Full article
(This article belongs to the Special Issue The Role of Interleukin in Health and Diseases)
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Article
Biomarkers for Comorbidities Modulate the Activity of T-Cells in COPD
Int. J. Mol. Sci. 2021, 22(13), 7187; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22137187 - 02 Jul 2021
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Abstract
In smoking-induced chronic obstructive pulmonary disease (COPD), various comorbidities are linked to systemic inflammation and infection-induced exacerbations. The underlying mechanisms are unclear but might provide therapeutic targets. T-cell activity is central in systemic inflammation and for infection-defense mechanisms and might be influenced by [...] Read more.
In smoking-induced chronic obstructive pulmonary disease (COPD), various comorbidities are linked to systemic inflammation and infection-induced exacerbations. The underlying mechanisms are unclear but might provide therapeutic targets. T-cell activity is central in systemic inflammation and for infection-defense mechanisms and might be influenced by comorbidities. Hypothesis: Circulating biomarkers of comorbidities modulate the activity of T-cells of the T-helper type 1 (Th1) and/or T-cytotoxic type 1 (Tc1). T-cells in peripheral blood mononuclear cells (PBMCs) from non-smokers (NS), current smokers without COPD (S), and COPD subjects (total n = 34) were ex vivo activated towards Th1/Tc1 and were then stimulated with biomarkers for metabolic and/or cardiovascular comorbidities (Brain Natriuretic Peptide, BNP; chemokine (C-C motif) ligand 18, CCL18; C-X3-C motif chemokine ligand 1, CX3CL1; interleukin-18, IL-18) or for asthma- and/or cancer-related comorbidities (CCL22; epidermal growth factor, EGF; IL-17; periostin) each at 10 or 50 ng/mL. The Th1/Tc1 activation markers interferon-γ (IFNγ), tumor necrosis factor-α (TNFα), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were analyzed in culture supernatants by Enzyme-Linked Immunosorbent Assay (ELISA). Ex-vivo activation induced IFNγ and TNFα without differences between the groups but GM-CSF more in S vs. NS. At 10 ng/mL, the different biomarkers increased or reduced the T-cell activation markers without a clear trend for one direction in the different categories of comorbidities or for the different T-cell activation markers. At 50 ng/mL, there was a clear shift towards suppressive effects, particularly for the asthma— and cancer-related biomarkers and in cells of S and COPD. Comorbidities might suppress T-cell immunity in COPD. This could explain the association of comorbidities with frequent exacerbations. Full article
(This article belongs to the Special Issue The Role of Interleukin in Health and Diseases)
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Review

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Review
Crosstalk between Metabolic Disorders and Immune Cells
Int. J. Mol. Sci. 2021, 22(18), 10017; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221810017 (registering DOI) - 16 Sep 2021
Viewed by 168
Abstract
Metabolic syndrome results from multiple risk factors that arise from insulin resistance induced by abnormal fat deposition. Chronic inflammation owing to obesity primarily results from the recruitment of pro-inflammatory M1 macrophages into the adipose tissue stroma, as the adipocytes within become hypertrophied. During [...] Read more.
Metabolic syndrome results from multiple risk factors that arise from insulin resistance induced by abnormal fat deposition. Chronic inflammation owing to obesity primarily results from the recruitment of pro-inflammatory M1 macrophages into the adipose tissue stroma, as the adipocytes within become hypertrophied. During obesity-induced inflammation in adipose tissue, pro-inflammatory cytokines are produced by macrophages and recruit further pro-inflammatory immune cells into the adipose tissue to boost the immune response. Here, we provide an overview of the biology of macrophages in adipose tissue and the relationship between other immune cells, such as CD4+ T cells, natural killer cells, and innate lymphoid cells, and obesity and type 2 diabetes. Finally, we discuss the link between the human pathology and immune response and metabolism and further highlight potential therapeutic targets for the treatment of metabolic disorders. Full article
(This article belongs to the Special Issue The Role of Interleukin in Health and Diseases)
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Review
Anti-Inflammatory Effect of Muscle-Derived Interleukin-6 and Its Involvement in Lipid Metabolism
Int. J. Mol. Sci. 2021, 22(18), 9889; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22189889 - 13 Sep 2021
Viewed by 244
Abstract
Interleukin (IL)-6 has been studied since its discovery for its role in health and diseases. It is one of the most important pro-inflammatory cytokines. IL-6 was reported as an exacerbating factor in coronavirus disease. In recent years, it has become clear that the [...] Read more.
Interleukin (IL)-6 has been studied since its discovery for its role in health and diseases. It is one of the most important pro-inflammatory cytokines. IL-6 was reported as an exacerbating factor in coronavirus disease. In recent years, it has become clear that the function of muscle-derived IL-6 is different from what has been reported so far. Exercise is accompanied by skeletal muscle contraction, during which, several bioactive substances, collectively named myokines, are secreted from the muscles. Many reports have shown that IL-6 is the most abundant myokine. Interestingly, it was indicated that IL-6 plays opposing roles as a myokine and as a pro-inflammatory cytokine. In this review, we discuss why IL-6 has different functions, the signaling mode of hyper-IL-6 via soluble IL-6 receptor (sIL-6R), and the involvement of soluble glycoprotein 130 in the suppressive effect of hyper-IL-6. Furthermore, the involvement of a disintegrin and metalloprotease family molecules in the secretion of sIL-6R is described. One of the functions of muscle-derived IL-6 is lipid metabolism in the liver. However, the differences between the functions of IL-6 as a pro-inflammatory cytokine and the functions of muscle-derived IL-6 are unclear. Although the involvement of myokines in lipid metabolism in adipocytes was previously discussed, little is known about the direct relationship between nonalcoholic fatty liver disease and muscle-derived IL-6. This review is the first to discuss the relationship between the function of IL-6 in diseases and the function of muscle-derived IL-6, focusing on IL-6 signaling and lipid metabolism in the liver. Full article
(This article belongs to the Special Issue The Role of Interleukin in Health and Diseases)
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Review
Interleukin-21 in Viral Infections
Int. J. Mol. Sci. 2021, 22(17), 9521; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22179521 - 01 Sep 2021
Viewed by 357
Abstract
Interleukin (IL)-21 is a cytokine that affects the differentiation and function of lymphoid and myeloid cells and regulates both innate and adaptive immune responses. In addition to regulating the immune response to tumor and viral infections, IL-21 also has a profound effect on [...] Read more.
Interleukin (IL)-21 is a cytokine that affects the differentiation and function of lymphoid and myeloid cells and regulates both innate and adaptive immune responses. In addition to regulating the immune response to tumor and viral infections, IL-21 also has a profound effect on the development of autoimmune and inflammatory diseases. IL-21 is produced mainly from CD4+ T cells—in particular, follicular helper T (Tfh) cells—which have a great influence on the regulation of antibody production. It is also an important cytokine for the activation of CD8+ T cells, and its role in recovering the function of CD8+ T cells exhausted by chronic microbial infections and cancer has been clarified. Thus, IL-21 plays an extremely important role in viral infections, especially chronic viral infections. In this review, I will introduce the findings to date on how IL-21 is involved in some typical viral infections and the potential of treating viral diseases with IL-21. Full article
(This article belongs to the Special Issue The Role of Interleukin in Health and Diseases)
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Review
Targeting Cytokines, Pathogen-Associated Molecular Patterns, and Damage-Associated Molecular Patterns in Sepsis via Blood Purification
Int. J. Mol. Sci. 2021, 22(16), 8882; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22168882 - 18 Aug 2021
Viewed by 514
Abstract
Sepsis is characterized by a dysregulated immune response to infections that causes life-threatening organ dysfunction and even death. When infections occur, bacterial cell wall components (endotoxin or lipopolysaccharide), known as pathogen-associated molecular patterns, bind to pattern recognition receptors, such as toll-like receptors, to [...] Read more.
Sepsis is characterized by a dysregulated immune response to infections that causes life-threatening organ dysfunction and even death. When infections occur, bacterial cell wall components (endotoxin or lipopolysaccharide), known as pathogen-associated molecular patterns, bind to pattern recognition receptors, such as toll-like receptors, to initiate an inflammatory response for pathogen elimination. However, strong activation of the immune system leads to cellular dysfunction and ultimately organ failure. Damage-associated molecular patterns (DAMPs), which are released by injured host cells, are well-recognized triggers that result in the elevation of inflammatory cytokine levels. A cytokine storm is thus amplified and sustained in this vicious cycle. Interestingly, during sepsis, neutrophils transition from powerful antimicrobial protectors into dangerous mediators of tissue injury and organ dysfunction. Thus, the concept of blood purification has evolved to include inflammatory cells and mediators. In this review, we summarize recent advances in knowledge regarding the role of lipopolysaccharides, cytokines, DAMPs, and neutrophils in the pathogenesis of sepsis. Additionally, we discuss the potential of blood purification, especially the adsorption technology, for removing immune cells and molecular mediators, thereby serving as a therapeutic strategy against sepsis. Finally, we describe the concept of our immune-modulating blood purification system. Full article
(This article belongs to the Special Issue The Role of Interleukin in Health and Diseases)
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