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Special Issue "Inflammatory Skin Conditions 2018"

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 2018).

Special Issue Editor

Prof. Dr. Christopher Jackson
Website
Guest Editor
Sutton Arthritis Research Laboratory, Kolling Institute, University of Sydney at Royal North Shore Hospital, Sydney, Australia
Interests: inflammation; chronic wounds; rheumatoid arthritis; skin; activated protein C; matrix metalloproteinases
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

The skin, the body's largest organ, provides a barrier to protect the body from environmental insults, including pathogens, as well as maintaining temperature, and control evaporation. This barrier is located in the outer layer of the skin known as the epidermis, which sits on the dermis. The epidermis is composed mainly of proliferating keratinocytes in the basal layer which differentiate as they migrate outwards to become lipid-bearing corneocytes. Breaches of this barrier are common events, however, the inability to restore this barrier function can result in health problems such as inflammatory skin conditions which are very common and have high morbidity. This group of diseases includes (in approximate increasing order of severity): Acne, which affects 50% of teenagers; rosacea which affects 10% of adults; atopic dermatitis which affects up to 20% population; and other less common but more serious diseases including psoriasis; chronic wounds, blistering diseases and toxic epidermal necrolysis. New and innovative drugs that dampen inflammation and restore the defective barrier are required to alleviate these recalcitrant conditions.

This Special Issue calls for original research, full reviews, and perspectives that address the progress and current knowledge in the overlapping research topics of inflammatory skin conditions. These include but are not limited to the fields that are mentioned in the keywords.

Prof. Dr. Christopher Jackson
Guest Editor

Manuscript Submission Information

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Keywords

  • inflammatory skin conditions
  • chronic wounds
  • psoriasis
  • dermatitis
  • epidermis
  • keratinocytes
  • barrier function
  • inflammatory cells
  • immunity

Related Special Issue

Published Papers (12 papers)

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Research

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Open AccessArticle
In Vitro Induction of T Helper 17 Cells by Synergistic Activation of Human Monocyte-Derived Langerhans Cell-Like Cells with Bacterial Agonists
Int. J. Mol. Sci. 2019, 20(6), 1367; https://doi.org/10.3390/ijms20061367 - 19 Mar 2019
Cited by 5
Abstract
In the case of epidermal barrier disruption, pathogens encounter skin-resident Langerhans cells (LCs) and are recognized by pathogen recognition receptors such as Toll-like receptors (TLRs). As the majority of microorganisms exhibit more than one TLR ligand, the mechanisms of subsequent T cell differentiation [...] Read more.
In the case of epidermal barrier disruption, pathogens encounter skin-resident Langerhans cells (LCs) and are recognized by pathogen recognition receptors such as Toll-like receptors (TLRs). As the majority of microorganisms exhibit more than one TLR ligand, the mechanisms of subsequent T cell differentiation are complex and far from clear. In this study, we investigated combinatory effects on Th cell polarization by bacterial cell wall compounds peptidoglycan (PGN) and lipopolysaccharide (LPS) and by bacterial nucleic acid (DNA). Expression of maturation markers CD40, CD80, HLA-DR and CCR7 and the release of IL-1β, IL-6 and IL-23 was strongly enhanced by simultaneous exposure to PGN, LPS and DNA in LCs. As all these factors were potential Th17 driving cytokines, we investigated the potency of combinatory TLR stimuli to induce Th17 cells via LC activation. High amounts of IL-17A and IL-22, key cytokines of Th17 cells, were detected. By intracellular costaining of IL-17+T cells, IL-22 (Th17) and IL-22+ (immature Th17) cells were identified. Interestingly, one population of LPS stimulated cells skewed into IL-9+Th cells, and LPS synergized with PGN while inducing high IL-22. In conclusion, our data indicates that when mediated by a fine-tuned signal integration via LCs, bacterial TLR agonists synergize and induce Th17 differentiation. Full article
(This article belongs to the Special Issue Inflammatory Skin Conditions 2018)
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Open AccessArticle
The Cutaneous Inflammatory Response to Thermal Burn Injury in a Murine Model
Int. J. Mol. Sci. 2019, 20(3), 538; https://doi.org/10.3390/ijms20030538 - 28 Jan 2019
Cited by 9
Abstract
Many burn interventions aim to target the inflammatory response as a means of enhancing healing or limiting hypertrophic scarring. Murine models of human burns have been developed, but the inflammatory response to injury in these models has not been well defined. The aim [...] Read more.
Many burn interventions aim to target the inflammatory response as a means of enhancing healing or limiting hypertrophic scarring. Murine models of human burns have been developed, but the inflammatory response to injury in these models has not been well defined. The aim of this study was to profile inflammatory cell populations and gene expression relative to healing and scarring in a murine model of thermal burns. Cutaneous injuries were created on the dorsal region of C57Bl/6 mice using a heated metal rod. Animals were euthanized at selected time points over ten weeks, with the lesions evaluated using macroscopic measurements, histology, immunofluorescent histochemistry and quantitative PCR. The burn method generated a reproducible, partial-thickness injury that healed within two weeks through both contraction and re-epithelialization, in a manner similar to human burns. The injury caused an immediate increase in pro-inflammatory cytokine and chemokine expression, coinciding with an influx of neutrophils, and the disappearance of Langerhans cells and mast cells. This preceded an influx of dendritic cells and macrophages, a quarter of which displayed an inflammatory (M1) phenotype, with both populations peaking at closure. As with human burns, the residual scar increased in size, epidermal and dermal thickness, and mast cell numbers over 10 weeks, but abnormal collagen I-collagen III ratios, fibre organization and macrophage populations resolved 3–4 weeks after closure. Characterisation of the inflammatory response in this promising murine burn model will assist future studies of burn complications and aid in the preclinical testing of new anti-inflammatory and anti-scarring therapies. Full article
(This article belongs to the Special Issue Inflammatory Skin Conditions 2018)
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Open AccessArticle
Periostin Links Skin Inflammation to Melanoma Progression in Humans and Mice
Int. J. Mol. Sci. 2019, 20(1), 169; https://doi.org/10.3390/ijms20010169 - 04 Jan 2019
Cited by 4
Abstract
It is widely accepted that chronic inflammation initiates and promotes carcinogenesis and tumor progression in various cell types. However, this paradigm has not been comprehensively investigated in melanoma. To investigate the effects of chronic inflammation on the progression of melanoma, we established a [...] Read more.
It is widely accepted that chronic inflammation initiates and promotes carcinogenesis and tumor progression in various cell types. However, this paradigm has not been comprehensively investigated in melanoma. To investigate the effects of chronic inflammation on the progression of melanoma, we established a murine inflammatory skin model and investigated the relationship between skin inflammation and melanoma progression. In a murine model, B16F10 melanoma cells in inflamed skin grew significantly more rapidly than cells in control skin. The stromal expression of periostin was upregulated in inflamed skin, and significantly more CD163+ M2 macrophages were recruited to the melanomas in inflamed skin. We then immunohistologically examined the expression of stromal periostin and the infiltration of CD163+ M2 macrophages in human acral lentiginous melanomas (n = 94) and analyzed the statistical associations with clinicopathological variables. In human melanomas, high periostin expression and a large number of infiltrated M2 macrophages were significantly correlated with poor prognosis. Furthermore, we confirmed that periostin promotes the proliferation of murine and human melanoma cells in vitro. Our findings indicate that periostin and M2 macrophages play a critical role in melanoma progression and prognosis in both humans and mice, indicating that periostin is a potential target for treating progressive melanoma. Full article
(This article belongs to the Special Issue Inflammatory Skin Conditions 2018)
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Open AccessArticle
A Microtube Array Membrane (MTAM) Encapsulated Live Fermenting Staphylococcus epidermidis as a Skin Probiotic Patch against Cutibacterium acnes
Int. J. Mol. Sci. 2019, 20(1), 14; https://doi.org/10.3390/ijms20010014 - 20 Dec 2018
Cited by 8
Abstract
Antibiotics without selectivity for acne treatment may destroy the beneficial microbes in the human microbiome that helps to fight Cutibacterium acnes (C. acnes), a bacterium associated with inflammatory acne vulgaris. Probiotic treatment by direct application of live Staphylococcus epidermidis (S. [...] Read more.
Antibiotics without selectivity for acne treatment may destroy the beneficial microbes in the human microbiome that helps to fight Cutibacterium acnes (C. acnes), a bacterium associated with inflammatory acne vulgaris. Probiotic treatment by direct application of live Staphylococcus epidermidis (S. epidermidis) onto the open acne lesions may run the risk of bloodstream infections. Here, we fabricated the polysulfone microtube array membranes (PSF MTAM) to encapsulate probiotic S. epidermidis. We demonstrate that the application of the encapsulation of S. epidermidis in PSF MTAM enhanced the glycerol fermentation activities of S. epidermidis. To mimic the granulomatous type of acne inflammatory acne vulgaris, the ears of mice were injected intradermally with C. acnes to induce the secretion of macrophage inflammatory protein-2 (MIP-2), a murine counterpart of human interleukin (IL)-8. The C. acnes-injected mouse ears were covered with a PST MTAM encapsulated with or without S. epidermidis in the presence of glycerol. The application of S. epidermidis-encapsulated PST MTAM plus glycerol onto the C. acnes-injected mouse ears considerably reduced the growth of C. acnes and the production of MIP-2. Furthermore, no S. epidermidis leaked from PSF MTAM into mouse skin. The S. epidermidis-encapsulated PST MTAM functions as a probiotic acne patch. Full article
(This article belongs to the Special Issue Inflammatory Skin Conditions 2018)
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Open AccessArticle
Topical Application of JAK1/JAK2 Inhibitor Momelotinib Exhibits Significant Anti-Inflammatory Responses in DNCB-Induced Atopic Dermatitis Model Mice
Int. J. Mol. Sci. 2018, 19(12), 3973; https://doi.org/10.3390/ijms19123973 - 10 Dec 2018
Cited by 5
Abstract
Atopic dermatitis (AD) is a chronic recurrent skin disease dominated by T-helper 2 inflammation. Momelotinib (MMB) is a novel JAK1/JAK2 inhibitor suppressing the signal transduction of multiple pro-inflammatory cytokines. Recent studies indicated that JAK inhibitor could play a therapeutic role in AD disease. [...] Read more.
Atopic dermatitis (AD) is a chronic recurrent skin disease dominated by T-helper 2 inflammation. Momelotinib (MMB) is a novel JAK1/JAK2 inhibitor suppressing the signal transduction of multiple pro-inflammatory cytokines. Recent studies indicated that JAK inhibitor could play a therapeutic role in AD disease. In this study, we evaluated the efficacy of MMB as a novel JAK1/JAK2 inhibitor in DNCB-induced AD mice and TSLP-activated dendritic cells. Our data showed that topical application of MMB reduced the skin severity scores and total serum IgE levels, and alleviated the histological indexes including epidermal thickness measurement and mast cell number. Also, it was demonstrated that MMB down-regulated the mRNA expression of IL-4, IL-5, IFN-γ and TSLP, and inhibited the phosphorylation of STAT1, STAT3 and STAT5 in skin lesions. Moreover, MMB reduced the expression of CD80, CD86, MHCII and mRNA of OX40L in TSLP-activated dendritic cells. In general, our study suggests that MMB can improve the symptoms of AD and topical application of MMB can become a promising new therapy strategy for AD. Full article
(This article belongs to the Special Issue Inflammatory Skin Conditions 2018)
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Open AccessArticle
Integrative Analysis of lncRNAs, miRNAs, and mRNA-Associated ceRNA Network in an Atopic Dermatitis Recurrence Model
Int. J. Mol. Sci. 2018, 19(10), 3263; https://doi.org/10.3390/ijms19103263 - 20 Oct 2018
Cited by 5
Abstract
Atopic dermatitis (AD) is a prevalent inflammatory skin disease characterized by its chronic nature and relapse. Ample evidence suggests that non-coding RNAs play a major role in AD pathogenesis. However, the mechanism remains unknown, particularly in AD recurrence. Dynamic morphological and cytokine changes [...] Read more.
Atopic dermatitis (AD) is a prevalent inflammatory skin disease characterized by its chronic nature and relapse. Ample evidence suggests that non-coding RNAs play a major role in AD pathogenesis. However, the mechanism remains unknown, particularly in AD recurrence. Dynamic morphological and cytokine changes were measured throughout the whole course of an FITC-induced AD recurrence murine model. Microarray assay and integrative analysis were performed to comprehensively explore long non-coding RNA (lncRNA), messenger RNA (mRNA), and microRNA (miRNA) networks. Our results showed that an AD recurrence model was established. Overall, 5766 lncRNAs, 4025 mRNAs, and 202 miRNAs changed after elicitation, whereas, 419 lncRNAs, 349 mRNAs, and more notably, only 23 miRNAs, were dysregulated in the remission phase. Gene ontology (GO) and KEGG pathway enrichment analyses were used to investigate the potential functions of the dysregulated genes. The altered regulation of seven miRNAs and seven lncRNAs were validated in different stages of the model. The competing endogenous RNA (ceRNA) network inferred that lncRNA humanlincRNA0490+ could compete for miR-155-5p binding, through which it might affect Pkiα expression. Altogether, our findings have provided a novel perspective on the potential roles of non-coding RNAs in AD, and suggest that specific non-coding RNAs could be new therapeutic targets against AD recurrence. Full article
(This article belongs to the Special Issue Inflammatory Skin Conditions 2018)
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Review

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Open AccessReview
The Dynamics of the Skin’s Immune System
Int. J. Mol. Sci. 2019, 20(8), 1811; https://doi.org/10.3390/ijms20081811 - 12 Apr 2019
Cited by 16
Abstract
The skin is a complex organ that has devised numerous strategies, such as physical, chemical, and microbiological barriers, to protect the host from external insults. In addition, the skin contains an intricate network of immune cells resident to the tissue, crucial for host [...] Read more.
The skin is a complex organ that has devised numerous strategies, such as physical, chemical, and microbiological barriers, to protect the host from external insults. In addition, the skin contains an intricate network of immune cells resident to the tissue, crucial for host defense as well as tissue homeostasis. In the event of an insult, the skin-resident immune cells are crucial not only for prevention of infection but also for tissue reconstruction. Deregulation of immune responses often leads to impaired healing and poor tissue restoration and function. In this review, we will discuss the defensive components of the skin and focus on the function of skin-resident immune cells in homeostasis and their role in wound healing. Full article
(This article belongs to the Special Issue Inflammatory Skin Conditions 2018)
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Open AccessReview
Psoriasis Pathogenesis and Treatment
Int. J. Mol. Sci. 2019, 20(6), 1475; https://doi.org/10.3390/ijms20061475 - 23 Mar 2019
Cited by 85
Abstract
Research on psoriasis pathogenesis has largely increased knowledge on skin biology in general. In the past 15 years, breakthroughs in the understanding of the pathogenesis of psoriasis have been translated into targeted and highly effective therapies providing fundamental insights into the pathogenesis of [...] Read more.
Research on psoriasis pathogenesis has largely increased knowledge on skin biology in general. In the past 15 years, breakthroughs in the understanding of the pathogenesis of psoriasis have been translated into targeted and highly effective therapies providing fundamental insights into the pathogenesis of chronic inflammatory diseases with a dominant IL-23/Th17 axis. This review discusses the mechanisms involved in the initiation and development of the disease, as well as the therapeutic options that have arisen from the dissection of the inflammatory psoriatic pathways. Our discussion begins by addressing the inflammatory pathways and key cell types initiating and perpetuating psoriatic inflammation. Next, we describe the role of genetics, associated epigenetic mechanisms, and the interaction of the skin flora in the pathophysiology of psoriasis. Finally, we include a comprehensive review of well-established widely available therapies and novel targeted drugs. Full article
(This article belongs to the Special Issue Inflammatory Skin Conditions 2018)
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Open AccessReview
IL-36, IL-37, and IL-38 Cytokines in Skin and Joint Inflammation: A Comprehensive Review of Their Therapeutic Potential
Int. J. Mol. Sci. 2019, 20(6), 1257; https://doi.org/10.3390/ijms20061257 - 13 Mar 2019
Cited by 12
Abstract
The interleukin (IL)-1 family of cytokines is composed of 11 members, including the most recently discovered IL-36α, β, γ, IL-37, and IL-38. Similar to IL-1, IL-36 cytokines are initiators and amplifiers of inflammation, whereas both IL-37 and IL-38 display anti-inflammatory activities. A few [...] Read more.
The interleukin (IL)-1 family of cytokines is composed of 11 members, including the most recently discovered IL-36α, β, γ, IL-37, and IL-38. Similar to IL-1, IL-36 cytokines are initiators and amplifiers of inflammation, whereas both IL-37 and IL-38 display anti-inflammatory activities. A few studies have outlined the role played by these cytokines in several inflammatory diseases. For instance, IL-36 agonists seem to be relevant for the pathogenesis of skin psoriasis whereas, despite being expressed within the synovial tissue, their silencing or overexpression do not critically influence the course of arthritis in mice. In this review, we will focus on the state of the art of the molecular features and biological roles of IL-36, IL-37, and IL-38 in representative skin- and joint-related inflammatory diseases, namely psoriasis, rheumatoid arthritis, and psoriatic arthritis. We will then offer an overview of the therapeutic potential of targeting the IL-36 axis in these diseases, either by blocking the proinflammatory agonists or enhancing the physiologic inhibitory feedback on the inflammation mediated by the antagonists IL-37 and IL-38. Full article
(This article belongs to the Special Issue Inflammatory Skin Conditions 2018)
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Open AccessReview
Activated Protein C in Cutaneous Wound Healing: From Bench to Bedside
Int. J. Mol. Sci. 2019, 20(4), 903; https://doi.org/10.3390/ijms20040903 - 19 Feb 2019
Cited by 4
Abstract
Independent of its well-known anticoagulation effects, activated protein C (APC) exhibits pleiotropic cytoprotective properties. These include anti-inflammatory actions, anti-apoptosis, and endothelial and epithelial barrier stabilisation. Such beneficial effects have made APC an attractive target of research in a plethora of physiological and pathophysiological [...] Read more.
Independent of its well-known anticoagulation effects, activated protein C (APC) exhibits pleiotropic cytoprotective properties. These include anti-inflammatory actions, anti-apoptosis, and endothelial and epithelial barrier stabilisation. Such beneficial effects have made APC an attractive target of research in a plethora of physiological and pathophysiological processes. Of note, the past decade or so has seen the emergence of its roles in cutaneous wound healing—a complex process involving inflammation, proliferation and remodelling. This review will highlight APC’s functions and mechanisms, and detail its pre-clinical and clinical studies on cutaneous wound healing. Full article
(This article belongs to the Special Issue Inflammatory Skin Conditions 2018)
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Open AccessReview
New Cytokines in the Pathogenesis of Atopic Dermatitis—New Therapeutic Targets
Int. J. Mol. Sci. 2018, 19(10), 3086; https://doi.org/10.3390/ijms19103086 - 09 Oct 2018
Cited by 26
Abstract
Atopic dermatitis (AD) is a recurrent, chronic, and inflammatory skin disease, which processes with severe itchiness. It often coexists with different atopic diseases. The number of people suffering from AD is relatively high. Epidemiological research demonstrates that 15–30% of children and 2–10% adults [...] Read more.
Atopic dermatitis (AD) is a recurrent, chronic, and inflammatory skin disease, which processes with severe itchiness. It often coexists with different atopic diseases. The number of people suffering from AD is relatively high. Epidemiological research demonstrates that 15–30% of children and 2–10% adults suffer from AD. The disease has significant negative social and economic impacts, substantially decreasing the quality of life of the patients and their families. Thanks to enormous progress in science and technology, it becomes possible to recognise complex genetic, immunological, and environmental factors and epidermal barrier defects that play a role in the pathogenesis of AD. We hope that the new insight on cytokines in AD will lead to new, individualised therapy and will open different therapeutic possibilities. In this article, we will focus on the cytokines, interleukin (IL)-17, IL-19, IL-33, and TSLP (thymic stromal lymphopoietin), which play a significant role in AD pathogenesis and may become the targets for future biologic therapies in AD. It is believed that the new era of biological drugs in AD will give a chance for patients to receive more successful treatment. Full article
(This article belongs to the Special Issue Inflammatory Skin Conditions 2018)
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Other

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Open AccessCommentary
Skin Sensitization Testing—What’s Next?
Int. J. Mol. Sci. 2019, 20(3), 666; https://doi.org/10.3390/ijms20030666 - 04 Feb 2019
Cited by 3
Abstract
There is an increasing demand for alternative in vitro methods to replace animal testing, and, to succeed, new methods are required to be at least as accurate as existing in vivo tests. However, skin sensitization is a complex process requiring coordinated and tightly [...] Read more.
There is an increasing demand for alternative in vitro methods to replace animal testing, and, to succeed, new methods are required to be at least as accurate as existing in vivo tests. However, skin sensitization is a complex process requiring coordinated and tightly regulated interactions between a variety of cells and molecules. Consequently, there is considerable difficulty in reproducing this level of biological complexity in vitro, and as a result the development of non-animal methods has posed a major challenge. However, with the use of a relevant biological system, the high information content of whole genome expression, and comprehensive bioinformatics, assays for most complex biological processes can be achieved. We propose that the Genomic Allergen Rapid Detection (GARD™) assay, developed to create a holistic data-driven in vitro model with high informational content, could be such an example. Based on the genomic expression of a mature human dendritic cell line and state-of-the-art machine learning techniques, GARD™ can today accurately predict skin sensitizers and correctly categorize skin sensitizing potency. Consequently, by utilizing advanced processing tools in combination with high information genomic or proteomic data, we can take the next step toward alternative methods with the same predictive accuracy as today’s in vivo methods—and beyond. Full article
(This article belongs to the Special Issue Inflammatory Skin Conditions 2018)
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