Roles of Cytokines in Skin Inflammation

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Tissues and Organs".

Deadline for manuscript submissions: closed (31 January 2024) | Viewed by 6645

Special Issue Editor

Special Issue Information

Dear Colleagues,

The skin, the largest organ in the human body, primarily protects against harmful environmental influences and prevents dehydration; thus, it represents the first barrier against physical, biological and chemical stress. To maintain this function, keratinocytes undergo a differentiation process that culminates in the generation of corneocytes. Keratinocytes and other resident skin cells produce cytokines that are responsible for controlling cellular communication. Cytokines are intercellular signalling proteins that serve as key modulators of the immune system and inflammation and initiate their biological action by interacting with target cells bearing cytokine receptors, initiating a cascade of cellular interactions. Cytokine signalling can result in multiple consequences for the skin’s barrier function. Certain inflammatory skin diseases are associated with cytokine overproduction, dysregulation and alteration in their receptors. It is likely that cytokines contribute to the pathogenesis of many inflammatory skin diseases; for example, cytokines influence keratinocyte proliferation and differentiation, at least in part by modulating the gene expression program in these cells. One consequence is the expressional control of other cytokines, resulting in a complex network of signalling molecules that affect keratinocytes’ physiology and the quality of the skin barrier. Deregulated cytokine expression can thus contribute to epidermal barrier dysfunction, as observed in many diseases, including atopic dermatitis (AD), allergic contact dermatitis and psoriasis. This Special Issue summarizes the current knowledge on cytokines and their functions in healthy skin and contributions to inflammatory skin diseases.

Dr. Maria Antonietta Panaro
Guest Editor

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Keywords

  • skin barrier
  • cytokine
  • cornification
  • atopic dermatitis
  • psoriasis
  • interleukin
  • keratinocytes

Published Papers (5 papers)

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Research

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24 pages, 7280 KiB  
Article
Unraveling Transcriptome Profile, Epigenetic Dynamics, and Morphological Changes in Psoriasis-like Keratinocytes: “Insights into Similarity with Psoriatic Lesional Epidermis”
by Ameneh Ghaffarinia, Szilárd Póliska, Ferhan Ayaydin, Aniko Goblos, Shahram Parvaneh, Máté Manczinger, Fanni Balogh, Lilla Erdei, Zoltán Veréb, Kornélia Szabó, Zsuzsanna Bata-Csörgő and Lajos Kemény
Cells 2023, 12(24), 2825; https://doi.org/10.3390/cells12242825 - 12 Dec 2023
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Abstract
Keratinocytes are one of the primary cells affected by psoriasis inflammation. Our study aimed to delve deeper into their morphology, transcriptome, and epigenome changes in response to psoriasis-like inflammation. We created a novel cytokine mixture to mimic mild and severe psoriasis-like inflammatory conditions [...] Read more.
Keratinocytes are one of the primary cells affected by psoriasis inflammation. Our study aimed to delve deeper into their morphology, transcriptome, and epigenome changes in response to psoriasis-like inflammation. We created a novel cytokine mixture to mimic mild and severe psoriasis-like inflammatory conditions in cultured keratinocytes. Upon induction of inflammation, we observed that the keratinocytes exhibited a mesenchymal-like phenotype, further confirmed by increased VIM mRNA expression and results obtained from confocal microscopy. We performed RNA sequencing to achieve a more global view, revealing 858 and 6987 DEGs in mildly and severely inflamed keratinocytes, respectively. Surprisingly, we found that the transcriptome of mildly inflamed keratinocytes more closely mimicked that of the psoriatic epidermis transcriptome than the severely inflamed keratinocytes. Genes involved in the IL-17 pathway were a major contributor to the similarities of the transcriptomes between mildly inflamed KCs and psoriatic epidermis. Mild and severe inflammation led to the gene regulation of epigenetic modifiers such as HATs, HDACs, DNMTs, and TETs. Immunofluorescence staining revealed distinct 5-hmC patterns in inflamed versus control keratinocytes, and consistently low 5-mC intensity in both groups. However, the global DNA methylation assay detected a tendency of decreased 5-mC levels in inflamed keratinocytes versus controls. This study emphasizes how inflammation severity affects the transcriptomic similarity of keratinocytes to psoriatic epidermis and proves dynamic epigenetic regulation and adaptive morphological changes in inflamed keratinocytes. Full article
(This article belongs to the Special Issue Roles of Cytokines in Skin Inflammation)
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Review

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17 pages, 2764 KiB  
Review
An OX-Tra’Ordinary Tale: The Role of OX40 and OX40L in Atopic Dermatitis
by Kaviyon Sadrolashrafi, Lily Guo, Robin Kikuchi, Audrey Hao, Rebecca K. Yamamoto, Hannah C. Tolson, Sara N. Bilimoria, Danielle K. Yee and April W. Armstrong
Cells 2024, 13(7), 587; https://doi.org/10.3390/cells13070587 - 28 Mar 2024
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Abstract
The transmembrane glycoprotein OX40 receptor (OX40) and its ligand, OX40L, are instrumental modulators of the adaptive immune response in humans. OX40 functions as a costimulatory molecule that promotes T cell activation, differentiation, and survival through ligation with OX40L. T cells play an integral [...] Read more.
The transmembrane glycoprotein OX40 receptor (OX40) and its ligand, OX40L, are instrumental modulators of the adaptive immune response in humans. OX40 functions as a costimulatory molecule that promotes T cell activation, differentiation, and survival through ligation with OX40L. T cells play an integral role in the pathogenesis of several inflammatory skin conditions, including atopic dermatitis (AD). In particular, T helper 2 (TH2) cells strongly contribute to AD pathogenesis via the production of cytokines associated with type 2 inflammation (e.g., IL-4, IL-5, IL-13, and IL-31) that lead to skin barrier dysfunction and pruritus. The OX40-OX40L interaction also promotes the activation and proliferation of other T helper cell populations (e.g., TH1, TH22, and TH17), and AD patients have demonstrated higher levels of OX40 expression on peripheral blood mononuclear cells than healthy controls. As such, the OX40-OX40L pathway is a potential target for AD treatment. Novel therapies targeting the OX40 pathway are currently in development, several of which have demonstrated promising safety and efficacy results in patients with moderate-to-severe AD. Herein, we review the function of OX40 and the OX40-OX40L signaling pathway, their role in AD pathogenesis, and emerging therapies targeting OX40-OX40L that may offer insights into the future of AD management. Full article
(This article belongs to the Special Issue Roles of Cytokines in Skin Inflammation)
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20 pages, 1460 KiB  
Review
Inflammatory Skin Diseases: Focus on the Role of Suppressors of Cytokine Signaling (SOCS) Proteins
by Antonia Cianciulli, Rosa Calvello, Chiara Porro, Dario Domenico Lofrumento and Maria Antonietta Panaro
Cells 2024, 13(6), 505; https://doi.org/10.3390/cells13060505 - 13 Mar 2024
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Abstract
Inflammatory skin diseases include a series of disorders characterized by a strong activation of the innate and adaptive immune system in which proinflammatory cytokines play a fundamental role in supporting inflammation. Skin inflammation is a complex process influenced by various factors, including genetic [...] Read more.
Inflammatory skin diseases include a series of disorders characterized by a strong activation of the innate and adaptive immune system in which proinflammatory cytokines play a fundamental role in supporting inflammation. Skin inflammation is a complex process influenced by various factors, including genetic and environmental factors, characterized by the dysfunction of both immune and non-immune cells. Psoriasis (PS) and atopic dermatitis (AD) are the most common chronic inflammatory conditions of the skin whose pathogeneses are very complex and multifactorial. Both diseases are characterized by an immunological dysfunction involving a predominance of Th1 and Th17 cells in PS and of Th2 cells in AD. Suppressor of cytokine signaling (SOCS) proteins are intracellular proteins that control inflammatory responses by regulating various signaling pathways activated by proinflammatory cytokines. SOCS signaling is involved in the regulation and progression of inflammatory responses in skin-resident and non-resident immune cells, and recent data suggest that these negative modulators are dysregulated in inflammatory skin diseases such as PS and AD. This review focuses on the current understanding about the role of SOCS proteins in modulating the activity of inflammatory mediators implicated in the pathogenesis of inflammatory skin diseases such as PS and AD. Full article
(This article belongs to the Special Issue Roles of Cytokines in Skin Inflammation)
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15 pages, 964 KiB  
Review
Potential Role of IL-37 in Atopic Dermatitis
by Alicja Mesjasz, Magdalena Trzeciak, Jolanta Gleń and Marta Jaskulak
Cells 2023, 12(23), 2766; https://doi.org/10.3390/cells12232766 - 04 Dec 2023
Cited by 1 | Viewed by 1219
Abstract
Interleukin 37 (IL-37) is a recently discovered member of the IL-1 cytokine family that appears to have anti-inflammatory and immunosuppressive effects in various diseases. IL-37 acts as a dual-function cytokine, exerting its effect extracellularly by forming a complex with the receptors IL-18 α [...] Read more.
Interleukin 37 (IL-37) is a recently discovered member of the IL-1 cytokine family that appears to have anti-inflammatory and immunosuppressive effects in various diseases. IL-37 acts as a dual-function cytokine, exerting its effect extracellularly by forming a complex with the receptors IL-18 α (IL-18Rα) and IL-1R8 and transmitting anti-inflammatory signals, as well as intracellularly by interacting with Smad3, entering the nucleus, and inhibiting the transcription of pro-inflammatory genes. Consequently, IL-37 is linked to IL-18, which plays a role in the pathogenesis of atopic dermatitis (AD), consistent with our studies. Some isoforms of IL-37 are expressed by keratinocytes, monocytes, and other skin immune cells. IL-37 has been found to modulate the skewed T helper 2 (Th2) inflammation that is fundamental to the pathogenesis of AD. This review provides an up-to-date summary of the function of IL-37 in modulating the immune system and analyses its potential role in the pathogenesis of AD. Moreover, it speculates on IL-37’s hypothetical value as a therapeutic target in the treatment of AD. Full article
(This article belongs to the Special Issue Roles of Cytokines in Skin Inflammation)
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Other

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16 pages, 1155 KiB  
Systematic Review
Cytokines and Epidermal Lipid Abnormalities in Atopic Dermatitis: A Systematic Review
by Parth R. Upadhyay, Lucia Seminario-Vidal, Brian Abe, Cyrus Ghobadi and Jonathan T. Sims
Cells 2023, 12(24), 2793; https://doi.org/10.3390/cells12242793 - 08 Dec 2023
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Abstract
Atopic dermatitis (AD) is the most common chronic inflammatory skin disease and presents a major public health problem worldwide. It is characterized by a recurrent and/or chronic course of inflammatory skin lesions with intense pruritus. Its pathophysiologic features include barrier dysfunction, aberrant immune [...] Read more.
Atopic dermatitis (AD) is the most common chronic inflammatory skin disease and presents a major public health problem worldwide. It is characterized by a recurrent and/or chronic course of inflammatory skin lesions with intense pruritus. Its pathophysiologic features include barrier dysfunction, aberrant immune cell infiltration, and alterations in the microbiome that are associated with genetic and environmental factors. There is a complex crosstalk between these components, which is primarily mediated by cytokines. Epidermal barrier dysfunction is the hallmark of AD and is caused by the disruption of proteins and lipids responsible for establishing the skin barrier. To better define the role of cytokines in stratum corneum lipid abnormalities related to AD, we conducted a systematic review of biomedical literature in PubMed from its inception to 5 September 2023. Consistent with the dominant TH2 skewness seen in AD, type 2 cytokines were featured prominently as possessing a central role in epidermal lipid alterations in AD skin. The cytokines associated with TH1 and TH17 were also identified to affect barrier lipids. Considering the broad cytokine dysregulation observed in AD pathophysiology, understanding the role of each of these in lipid abnormalities and barrier dysfunction will help in developing therapeutics to best achieve barrier homeostasis in AD patients. Full article
(This article belongs to the Special Issue Roles of Cytokines in Skin Inflammation)
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