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Cytokine Receptors In Development, Homeostasis & Disease
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Cytokine Receptors In Development, Homeostasis & Disease

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 26183

Special Issue Editor

Prof. Dr. Alister C. Ward

E-Mail Website
Guest Editor
School of Medicine, Centre of Molecular and Medical Research, Deakin University, Waurn Ponds, VIC 3216, Australia
Interests: cytokines; cell signaling; JAK-STAT pathway; SOCS; hematopoiesis; leukocytes lymphocytes; leukemia; lymphoma
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The development, maintenance and regulation of specific cell lineages is both complex and critical, with disruptions of these processes implicated in a wide variety of disease states. There are many mechanisms via which such processes are regulated, including both intrinsic and extrinsic controls.

Cytokine receptors are expressed on the surface of responsive cells, where they can impact a multitude of cell functions following activation by a relevant cytokine. These signals are important for the normal development and function of many cell lineages, notably including blood and immune cells. Equally, they have been shown to be perturbed in many pathological states.

This Special Issue is a celebration of the cytokine receptor family, which will examine both their common and unique features, with a strong emphasis on their role in development and disease.

Prof. Alister C. Ward
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. 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

  • cytokines
  • cytokine receptors
  • JAK–-STAT pathway
  • immunology
  • hematology
  • development
  • cancer
  • infectious disease

Published Papers (7 papers)

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Editorial

Jump to: Research, Review

2 pages, 152 KiB  
Editorial
Cytokine Receptors in Development, Homeostasis and Disease
by Alister C. Ward
Int. J. Mol. Sci. 2023, 24(12), 10352; https://doi.org/10.3390/ijms241210352 - 19 Jun 2023
Viewed by 732
Abstract
This Special Issue represents a collective celebration of the cytokine receptor superfamily and the myriad of functions mediated by these important molecules in development and homeostasis, as well as their disruption in disease [...] Full article
(This article belongs to the Special Issue Cytokine Receptors In Development, Homeostasis & Disease)

Research

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13 pages, 4617 KiB  
Article
Generation and Characterization of a Zebrafish IL-2Rγc SCID Model
by Robert Sertori, Realla Jones, Faiza Basheer, Leni Rivera, Samantha Dawson, Stella Loke, Somayyeh Heidary, Amardeep Dhillon, Clifford Liongue and Alister C. Ward
Int. J. Mol. Sci. 2022, 23(4), 2385; https://doi.org/10.3390/ijms23042385 - 21 Feb 2022
Cited by 14 | Viewed by 2187
Abstract
The IL-2 family of cytokines act via receptor complexes that share the interleukin-2 receptor gamma common (IL-2Rγc) chain to play key roles in lymphopoiesis. Inactivating IL-2Rγc mutations results in severe combined immunodeficiency (SCID) in humans and other species. This study sought to generate [...] Read more.
The IL-2 family of cytokines act via receptor complexes that share the interleukin-2 receptor gamma common (IL-2Rγc) chain to play key roles in lymphopoiesis. Inactivating IL-2Rγc mutations results in severe combined immunodeficiency (SCID) in humans and other species. This study sought to generate an equivalent zebrafish SCID model. The zebrafish il2rga gene was targeted for genome editing using TALENs and presumed loss-of-function alleles analyzed with respect to immune cell development and impacts on intestinal microbiota and tumor immunity. Knockout of zebrafish Il-2rγc.a resulted in a SCID phenotype, including a significant reduction in T cells, with NK cells also impacted. This resulted in dysregulated intestinal microbiota and defective immunity to tumor xenotransplants. Collectively, this establishes a useful zebrafish SCID model. Full article
(This article belongs to the Special Issue Cytokine Receptors In Development, Homeostasis & Disease)
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16 pages, 3895 KiB  
Article
Protein PGLYRP1/Tag7 Peptides Decrease the Proinflammatory Response in Human Blood Cells and Mouse Model of Diffuse Alveolar Damage of Lung through Blockage of the TREM-1 and TNFR1 Receptors
by Tatiana N. Sharapova, Elena A. Romanova, Aleksandr S. Chernov, Alexey N. Minakov, Vitaly A. Kazakov, Anna A. Kudriaeva, Alexey A. Belogurov, Jr., Olga K. Ivanova, Alexander G. Gabibov, Georgii B. Telegin, Denis V. Yashin and Lidia P. Sashchenko
Int. J. Mol. Sci. 2021, 22(20), 11213; https://doi.org/10.3390/ijms222011213 - 18 Oct 2021
Cited by 10 | Viewed by 2520
Abstract
Infection caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2) in many cases is accompanied by the release of a large amount of proinflammatory cytokines in an event known as “cytokine storm”, which is associated with severe coronavirus disease 2019 (COVID-19) cases and [...] Read more.
Infection caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2) in many cases is accompanied by the release of a large amount of proinflammatory cytokines in an event known as “cytokine storm”, which is associated with severe coronavirus disease 2019 (COVID-19) cases and high mortality. The excessive production of proinflammatory cytokines is linked, inter alia, to the enhanced activity of receptors capable of recognizing the conservative regions of pathogens and cell debris, namely TLRs, TREM-1 and TNFR1. Here we report that peptides derived from innate immunity protein Tag7 inhibit activation of TREM-1 and TNFR1 receptors during acute inflammation. Peptides from the N-terminal fragment of Tag7 bind only to TREM-1, while peptides from the C-terminal fragment interact solely with TNFR1. Selected peptides are capable of inhibiting the production of proinflammatory cytokines both in peripheral blood mononuclear cells (PBMCs) from healthy donors and in vivo in the mouse model of acute lung injury (ALI) by diffuse alveolar damage (DAD). Treatment with peptides significantly decreases the infiltration of mononuclear cells to lungs in animals with DAD. Our findings suggest that Tag7-derived peptides might be beneficial in terms of the therapy or prevention of acute lung injury, e.g., for treating COVID-19 patients with severe pulmonary lesions. Full article
(This article belongs to the Special Issue Cytokine Receptors In Development, Homeostasis & Disease)
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Review

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24 pages, 8655 KiB  
Review
The Role of Oncostatin M and Its Receptor Complexes in Cardiomyocyte Protection, Regeneration, and Failure
by Thomas Kubin, Praveen Gajawada, Peter Bramlage, Stefan Hein, Benedikt Berge, Ayse Cetinkaya, Heiko Burger, Markus Schönburg, Wolfgang Schaper, Yeong-Hoon Choi and Manfred Richter
Int. J. Mol. Sci. 2022, 23(3), 1811; https://doi.org/10.3390/ijms23031811 - 05 Feb 2022
Cited by 10 | Viewed by 5697
Abstract
Oncostatin M (OSM), a member of the interleukin-6 family, functions as a major mediator of cardiomyocyte remodeling under pathological conditions. Its involvement in a variety of human cardiac diseases such as aortic stenosis, myocardial infarction, myocarditis, cardiac sarcoidosis, and various cardiomyopathies make the [...] Read more.
Oncostatin M (OSM), a member of the interleukin-6 family, functions as a major mediator of cardiomyocyte remodeling under pathological conditions. Its involvement in a variety of human cardiac diseases such as aortic stenosis, myocardial infarction, myocarditis, cardiac sarcoidosis, and various cardiomyopathies make the OSM receptor (OSMR) signaling cascades a promising therapeutic target. However, the development of pharmacological treatment strategies is highly challenging for many reasons. In mouse models of heart disease, OSM elicits opposing effects via activation of the type II receptor complex (OSMR/gp130). Short-term activation of OSMR/gp130 protects the heart after acute injury, whereas chronic activation promotes the development of heart failure. Furthermore, OSM has the ability to integrate signals from unrelated receptors that enhance fetal remodeling (dedifferentiation) of adult cardiomyocytes. Because OSM strongly stimulates the production and secretion of extracellular proteins, it is likely to exert systemic effects, which in turn, could influence cardiac remodeling. Compared with the mouse, the complexity of OSM signaling is even greater in humans because this cytokine also activates the type I leukemia inhibitory factor receptor complex (LIFR/gp130). In this article, we provide an overview of OSM-induced cardiomyocyte remodeling and discuss the consequences of OSMR/gp130 and LIFR/gp130 activation under acute and chronic conditions. Full article
(This article belongs to the Special Issue Cytokine Receptors In Development, Homeostasis & Disease)
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20 pages, 791 KiB  
Review
Role of the Interaction of Tumor Necrosis Factor-α and Tumor Necrosis Factor Receptors 1 and 2 in Bone-Related Cells
by Hideki Kitaura, Aseel Marahleh, Fumitoshi Ohori, Takahiro Noguchi, Yasuhiko Nara, Adya Pramusita, Ria Kinjo, Jinghan Ma, Kayoko Kanou and Itaru Mizoguchi
Int. J. Mol. Sci. 2022, 23(3), 1481; https://doi.org/10.3390/ijms23031481 - 27 Jan 2022
Cited by 28 | Viewed by 5921
Abstract
Tumor necrosis factor-α (TNF-α) is a pleiotropic cytokine expressed by macrophages, monocytes, and T cells, and its expression is triggered by the immune system in response to pathogens and their products, such as endotoxins. TNF-α plays an important role in host defense by [...] Read more.
Tumor necrosis factor-α (TNF-α) is a pleiotropic cytokine expressed by macrophages, monocytes, and T cells, and its expression is triggered by the immune system in response to pathogens and their products, such as endotoxins. TNF-α plays an important role in host defense by inducing inflammatory reactions such as phagocytes and cytocidal systems activation. TNF-α also plays an important role in bone metabolism and is associated with inflammatory bone diseases. TNF-α binds to two cell surface receptors, the 55kDa TNF receptor-1 (TNFR1) and the 75kDa TNF receptor-2 (TNFR2). Bone is in a constant state of turnover; it is continuously degraded and built via the process of bone remodeling, which results from the regulated balance between bone-resorbing osteoclasts, bone-forming osteoblasts, and the mechanosensory cell type osteocytes. Precise interactions between these cells maintain skeletal homeostasis. Studies have shown that TNF-α affects bone-related cells via TNFRs. Signaling through either receptor results in different outcomes in different cell types as well as in the same cell type. This review summarizes and discusses current research on the TNF-α and TNFR interaction and its role in bone-related cells. Full article
(This article belongs to the Special Issue Cytokine Receptors In Development, Homeostasis & Disease)
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31 pages, 4948 KiB  
Review
Cytokine Receptors—Regulators of Antimycobacterial Immune Response
by Magdalena Druszczyńska, Magdalena Godkowicz, Jakub Kulesza, Sebastian Wawrocki and Marek Fol
Int. J. Mol. Sci. 2022, 23(3), 1112; https://doi.org/10.3390/ijms23031112 - 20 Jan 2022
Cited by 9 | Viewed by 4505
Abstract
Cytokine receptors are critical regulators of the antimycobacterial immune response, playing a key role in initiating and coordinating the recruitment and activation of immune cells during infection. They recognize and bind specific cytokines and are involved in inducing intracellular signal transduction pathways that [...] Read more.
Cytokine receptors are critical regulators of the antimycobacterial immune response, playing a key role in initiating and coordinating the recruitment and activation of immune cells during infection. They recognize and bind specific cytokines and are involved in inducing intracellular signal transduction pathways that regulate a diverse range of biological functions, including proliferation, differentiation, metabolism and cell growth. Due to mutations in cytokine receptor genes, defective signaling may contribute to increased susceptibility to mycobacteria, allowing the pathogens to avoid killing and immune surveillance. This paper provides an overview of cytokine receptors important for the innate and adaptive immune responses against mycobacteria and discusses the implications of receptor gene defects for the course of mycobacterial infection. Full article
(This article belongs to the Special Issue Cytokine Receptors In Development, Homeostasis & Disease)
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24 pages, 10058 KiB  
Review
CRLF1 and CLCF1 in Development, Health and Disease
by Laura Crisponi, Insa Buers and Frank Rutsch
Int. J. Mol. Sci. 2022, 23(2), 992; https://doi.org/10.3390/ijms23020992 - 17 Jan 2022
Cited by 9 | Viewed by 3601
Abstract
Cytokines and their receptors have a vital function in regulating various processes such as immune function, inflammation, haematopoiesis, cell growth and differentiation. The interaction between a cytokine and its specific receptor triggers intracellular signalling cascades that lead to altered gene expression in the [...] Read more.
Cytokines and their receptors have a vital function in regulating various processes such as immune function, inflammation, haematopoiesis, cell growth and differentiation. The interaction between a cytokine and its specific receptor triggers intracellular signalling cascades that lead to altered gene expression in the target cell and consequent changes in its proliferation, differentiation, or activation. In this review, we highlight the role of the soluble type I cytokine receptor CRLF1 (cytokine receptor-like factor-1) and the Interleukin (IL)-6 cytokine CLCF1 (cardiotrophin-like cytokine factor 1) during development in physiological and pathological conditions with particular emphasis on Crisponi/cold-induced sweating syndrome (CS/CISS) and discuss new insights, challenges and possibilities arising from recent studies. Full article
(This article belongs to the Special Issue Cytokine Receptors In Development, Homeostasis & Disease)
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