Mechanisms Underlying Skin Pathologies

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Medical Research".

Deadline for manuscript submissions: closed (20 October 2021) | Viewed by 32769

Special Issue Editors


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Guest Editor
Department of Medical Chemistry, University of Debrecen, 4032 Debrecen, Hungary
Interests: lipid metabolism; skin; skin biology; sebaceous gland diseases; sebaceous glands; keratinocytes; human microbiome

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Guest Editor
Department of Immunology, University of Debrecen, 4032 Debrecen, Hungary
Interests: physiology; cell culture; cell signaling; signaling pathways; clinical dermatology; pruritus; neuroimmune communication; langerhans cells; cannabinoids and TRP channels

Special Issue Information

Dear Colleagues, 

The skin is our largest organ and the first protective barrier of the human body, as the skin is in direct contact with our environment. The skin is able to resist the invasion of harmful substances to the body and prevent the loss of moisture and electrolytes, provided its barrier is intact.  

Chronic disturbances in skin homeostasis can lead to the development of pathological conditions, such as acne vulgaris, rosacea, atopic dermatitis, psoriasis, hidradenitis suppurativa, etc. Though these are not life-threatening diseases, these pathologies strongly and negatively influence the quality of life of affected people and may have serious psychological consequences. Patients are often embarrassed about the appearance of their skin and have reduced levels of employment and income. The combined costs of long-term therapy and social costs of the disease have a major impact on healthcare systems and on society in general. However, therapeutic modalities are still extremely limited in these conditions.

The pathogenesis of skin diseases is extraordinarily complex. Therefore, more insight into the mechanisms underlying skin pathologies would be crucial in the identification of novel therapeutic targets that could help millions of patients.

This Special Issue calls for original research, full reviews, case studies, and perspectives that address the progress and current knowledge on skin diseases.

Dr. Magdolna Szanto
Dr. Attila Gabor Szollosi
Guest Editors

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Keywords

  • skin diseases
  • inflammation
  • skin microbiota
  • lipid barrier
  • psoriasis
  • acne vulgaris
  • atopic dermatitis
  • rosacea
  • hidradenitis suppurativa

Published Papers (9 papers)

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Research

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10 pages, 1178 KiB  
Communication
Antigen-Presenting Cells in Psoriasis
by Dóra Antal, Shahrzad Alimohammadi, Péter Bai, Attila Gábor Szöllősi and Magdolna Szántó
Life 2022, 12(2), 234; https://doi.org/10.3390/life12020234 - 3 Feb 2022
Cited by 6 | Viewed by 2778
Abstract
Psoriasis is classically considered a chronic inflammatory skin disorder, however the identification of autoantigens in its pathogenesis established it as a T cell mediated autoimmune disease. As such professional antigen-presenting cells (APCs) are key players in the development of lesions. APCs in the [...] Read more.
Psoriasis is classically considered a chronic inflammatory skin disorder, however the identification of autoantigens in its pathogenesis established it as a T cell mediated autoimmune disease. As such professional antigen-presenting cells (APCs) are key players in the development of lesions. APCs in the skin include dendritic cells, Langerhans cells and monocytes/macrophages. In addition, epidermal keratinocytes and dermal mast cells are also endowed with antigen-presenting capacity. Skin APCs have central role in the maintenance of cutaneous immune homeostasis, as well as in initiating and sustaining inflammation under pathologic conditions. In this review we discuss the functional specialization of human skin APCs that promote T cell activation and adaptive immune response during psoriasis initiation and onset. Full article
(This article belongs to the Special Issue Mechanisms Underlying Skin Pathologies)
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13 pages, 1335 KiB  
Article
Atopic Dermatitis Severity, Patient Perception of the Disease, and Personality Characteristics: How Are They Related to Quality of Life?
by Liborija Lugović-Mihić, Jelena Meštrović-Štefekov, Iva Ferček, Nives Pondeljak, Elvira Lazić-Mosler and Ana Gašić
Life 2021, 11(12), 1434; https://doi.org/10.3390/life11121434 - 20 Dec 2021
Cited by 5 | Viewed by 2820
Abstract
Introduction: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin condition that greatly affects patients’ quality of life, psychological condition, and social relationships. Materials And Methods: To analyze different aspects of AD patients’ quality of life, we used the SCORing Atopic Dermatitis (SCORAD) [...] Read more.
Introduction: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin condition that greatly affects patients’ quality of life, psychological condition, and social relationships. Materials And Methods: To analyze different aspects of AD patients’ quality of life, we used the SCORing Atopic Dermatitis (SCORAD) index (for AD severity), the Dermatology Life Quality Index (DLQI), the World Health Organization Quality of Life Brief Version (WHOQOL-BREF), the Brief Illness Perception Questionnaire (Brief IPQ), and the Crown–Crisp Experiential Index (CCEI) to analyze personality traits. The study included 84 AD patients, 42 with clinical manifestations and 42 in remission. Results: SCORAD values correlated positively and linearly with DLQI (r = 0.551; p < 0.001) and with disease impact on life, disease control, and disease symptoms (r = 0.350–0.398; p ≤ 0.023). DLQI was also related to certain personality characteristics (free-floating anxiety disorder, obsession, somatization, and depression (p ≤ 0.032)). Symptomatic AD patients had a significantly more impaired DLQI than asymptomatic patients (p < 0.001) and the two groups differed in some IPQ dimensions, but they did not differ significantly concerning the WHOQOL-BREF dimensions and personality traits (CCEI). Conclusion: Since AD patient quality of life was dependent not only on disease severity but was also influenced by patient personality characteristics (anxiety disorder, obsession, somatization, depression), many factors need to be taken into account to create effective, patient-specific therapy regimens. Full article
(This article belongs to the Special Issue Mechanisms Underlying Skin Pathologies)
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16 pages, 3122 KiB  
Article
Identification of Immune Function-Related Subtypes in Cutaneous Melanoma
by Lin Liu, Junkai Zhu, Tong Jin, Mengjia Huang, Yi Chen, Li Xu, Wenxuan Chen, Bo Jiang and Fangrong Yan
Life 2021, 11(9), 925; https://doi.org/10.3390/life11090925 - 6 Sep 2021
Cited by 1 | Viewed by 1753
Abstract
Tumour immunotherapy combined with molecular typing is a new therapy to help select patients. However, molecular typing algorithms related to tumour immune function have not been thoroughly explored. We herein proposed a single sample immune signature network (SING) method to identify new immune [...] Read more.
Tumour immunotherapy combined with molecular typing is a new therapy to help select patients. However, molecular typing algorithms related to tumour immune function have not been thoroughly explored. We herein proposed a single sample immune signature network (SING) method to identify new immune function-related subtypes of cutaneous melanoma of the skin. A sample-specific network and tumour microenvironment were constructed based on the immune annotation of cutaneous melanoma samples. Then, the differences and heterogeneity of immune function among different subtypes were analysed and verified. A total of 327 cases of cutaneous melanoma were divided into normal and immune classes; the immune class had more immune enrichment characteristics. After further subdividing the 327 cases into three immune-related subtypes, the degree of immune enrichment in the “high immune subtype” was greater than that in other subtypes. Similar results were validated in both tumour samples and cell lines. Sample-specific networks and the tumour microenvironment based on immune annotation contribute to the mining of cutaneous melanoma immune function-related subtypes. Mutations in B2M and PTEN are considered potential therapeutic targets that can improve the immune response. Patients with a high immune subtype can generally obtain a better immune prognosis effect, and the prognosis may be improved when combined with TGF-β inhibitors. Full article
(This article belongs to the Special Issue Mechanisms Underlying Skin Pathologies)
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12 pages, 2276 KiB  
Article
Morphological Alterations and Increased S100B Expression in Epidermal Langerhans Cells Detected in Skin from Patients with Progressive Vitiligo
by Fei Yang, Lingli Yang, Lanting Teng, Huimin Zhang and Ichiro Katayama
Life 2021, 11(6), 579; https://doi.org/10.3390/life11060579 - 18 Jun 2021
Cited by 3 | Viewed by 2449
Abstract
The role of Langerhans cells (LCs) in vitiligo pathogenesis remains unclear, with published studies reporting contradictory results regarding the quantity of LCs and no data on the features of LCs in vitiligo. Here, we aimed to analyze the presence, density, and morphological features [...] Read more.
The role of Langerhans cells (LCs) in vitiligo pathogenesis remains unclear, with published studies reporting contradictory results regarding the quantity of LCs and no data on the features of LCs in vitiligo. Here, we aimed to analyze the presence, density, and morphological features of LCs in the epidermis of patients with vitiligo. Skin biopsies were stained for LCs using anti-CD1a/anti-langerin antibodies and analyzed by immunocytochemistry with light and electron microscopy. Compared with healthy controls, we detected significantly increased numbers of epidermal LCs in lesional skin from vitiligo in the progressive state. These LCs exhibited striking morphological alterations, including an elevated number of dendrites, with increased length and more branches than dendrites from controls. Ultrastructure examination via immuno-electron microscopy revealed markedly reduced Birbeck granules (BGs) and shorter BG rods in LCs from progressive vitiligo, with higher expression of langerin. Additionally, expression of S100B, the activity biomarker of vitiligo, was increased in these LCs. This work provides new insight on the cellular composition of LCs in vitiliginous skin, revealing altered morphology and increased LC numbers, with elevated S100B expression. Our data suggest LCs might play a critical role in vitiligo pathogenesis and thus may represent a novel therapeutic target for this disease. Full article
(This article belongs to the Special Issue Mechanisms Underlying Skin Pathologies)
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18 pages, 3986 KiB  
Article
GLUT-1 Enhances Glycolysis, Oxidative Stress, and Fibroblast Proliferation in Keloid
by Ying-Yi Lu, Chieh-Hsin Wu, Chien-Hui Hong, Kee-Lung Chang and Chih-Hung Lee
Life 2021, 11(6), 505; https://doi.org/10.3390/life11060505 - 30 May 2021
Cited by 17 | Viewed by 4191
Abstract
A keloid is a fibroproliferative skin tumor. Proliferating keloid fibroblasts (KFs) demand active metabolic utilization. The contributing roles of glycolysis and glucose metabolism in keloid fibroproliferation remain unclear. This study aims to determine the regulation of glycolysis and glucose metabolism by glucose transporter-1 [...] Read more.
A keloid is a fibroproliferative skin tumor. Proliferating keloid fibroblasts (KFs) demand active metabolic utilization. The contributing roles of glycolysis and glucose metabolism in keloid fibroproliferation remain unclear. This study aims to determine the regulation of glycolysis and glucose metabolism by glucose transporter-1 (GLUT-1), an essential protein to initiate cellular glucose uptake, in keloids and in KFs. Tissues of keloids and healthy skin were explanted for KFs and normal fibroblasts (NFs), respectively. GLUT-1 expression was measured by immunofluorescence, RT-PCR, and immunoblotting. The oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were measured with or without WZB117, a GLUT-1 inhibitor. Reactive oxygen species (ROS) were assayed by MitoSOX immunostaining. The result showed that glycolysis (ECAR) was enhanced in KFs, whereas OCR was not. GLUT-1 expression was selectively increased in KFs. Consistently, GLUT-1 expression was increased in keloid tissue. Treatment with WZB117 abolished the enhanced ECAR, including glycolysis and glycolytic capacity, in KFs. ROS levels were increased in KFs compared to those in NFs. GLUT-1 inhibition suppressed not only the ROS levels but also the cell proliferation in KFs. In summary, the GLUT-1-dependent glycolysis and ROS production mediated fibroblast proliferation in keloids. GLUT1 might be a potential target for metabolic reprogramming to treat keloids. Full article
(This article belongs to the Special Issue Mechanisms Underlying Skin Pathologies)
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15 pages, 3468 KiB  
Article
Natural Sulfurs Inhibit LPS-Induced Inflammatory Responses through NF-κB Signaling in CCD-986Sk Skin Fibroblasts
by Nipin Sp, Dong Young Kang, Hyoung Do Kim, Alexis Rugamba, Eun Seong Jo, Jong-Chan Park, Se Won Bae, Jin-Moo Lee and Kyoung-Jin Jang
Life 2021, 11(5), 427; https://doi.org/10.3390/life11050427 - 10 May 2021
Cited by 8 | Viewed by 3906
Abstract
Lipopolysaccharide (LPS)-induced inflammatory response leads to serious damage, up to and including tumorigenesis. Natural mineral sulfur, non-toxic sulfur (NTS), and methylsulfonylmethane (MSM) have anti-inflammatory activity that may inhibit LPS-induced inflammation. We hypothesized that sulfur compounds could inhibit LPS-induced inflammatory responses in CCD-986Sk skin [...] Read more.
Lipopolysaccharide (LPS)-induced inflammatory response leads to serious damage, up to and including tumorigenesis. Natural mineral sulfur, non-toxic sulfur (NTS), and methylsulfonylmethane (MSM) have anti-inflammatory activity that may inhibit LPS-induced inflammation. We hypothesized that sulfur compounds could inhibit LPS-induced inflammatory responses in CCD-986Sk skin fibroblasts. We used Western blotting and real-time PCR to analyze molecular signaling in treated and untreated cultures. We also used flow cytometry for cell surface receptor analysis, comet assays to evaluate DNA damage, and ELISA-based cytokine detection. LPS induced TLR4 activation and NF-κB signaling via canonical and protein kinase C (PKC)-dependent pathways, while NTS and MSM downregulated that response. NTS and MSM also inhibited LPS-induced nuclear accumulation and binding of NF-κB to proinflammatory cytokines COX-2, IL-1β, and IL-6. Finally, the sulfur compounds suppressed LPS-induced ROS accumulation and DNA damage in CCD-986Sk cells. These results suggest that natural sulfur compounds could be used to treat inflammation and may be useful in the development of cosmetics. Full article
(This article belongs to the Special Issue Mechanisms Underlying Skin Pathologies)
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Review

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24 pages, 1698 KiB  
Review
Marked to Die-Cell Death Mechanisms for Keratinocyte Acantholysis in Pemphigus Diseases
by Valéria Bumiller-Bini Hoch, Larissa Schneider, Anna Elisabeth Pumpe, Emelie Lüders, Jennifer Elisabeth Hundt and Angelica Beate Winter Boldt
Life 2022, 12(3), 329; https://doi.org/10.3390/life12030329 - 22 Feb 2022
Cited by 1 | Viewed by 2556
Abstract
Pemphigus is a group of blistering autoimmune diseases causing painful skin lesions, characterized by acantholysis and by the production of autoantibodies against, mainly, adhesion proteins. We reviewed the literature for molecules and/ or features involved in the 12 cell death pathways described by [...] Read more.
Pemphigus is a group of blistering autoimmune diseases causing painful skin lesions, characterized by acantholysis and by the production of autoantibodies against, mainly, adhesion proteins. We reviewed the literature for molecules and/ or features involved in the 12 cell death pathways described by Nomenclature Committee on Cell Death, taking place in pemphigus patients, cell lines, or human skin organ cultures treated with sera or IgG from pemphigus patients or in pemphigus mouse models, and found 61 studies mentioning 97 molecules involved in cell death pathways. Among the molecules, most investigated were pleiotropic molecules such as TNF and CASP3, followed by FASL and CASP8, and then by FAS, BAX, BCL2, and TP53, all involved in more than one pathway but interpreted to function only within apoptosis. Most of these previous investigations focused only on apoptosis, but four recent studies, using TUNEL assays and/or electron microscopy, disqualified this pathway as a previous event of acantholysis. For PV, apoptolysis was suggested as a cell death mechanism based on pathogenic autoantibodies diversity, mitochondrial dysfunction, and p38 MAPK signaling. To answer those many questions that remain on cell death and pemphigus, we propose well-controlled, statistically relevant investigations on pemphigus and cell death pathways besides apoptosis, to overcome the challenges of understanding the etiopathology of pemphigus diseases. Full article
(This article belongs to the Special Issue Mechanisms Underlying Skin Pathologies)
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14 pages, 318 KiB  
Review
Features of the Skin Microbiota in Common Inflammatory Skin Diseases
by Iva Ferček, Liborija Lugović-Mihić, Arjana Tambić-Andrašević, Diana Ćesić, Ana Gverić Grginić, Iva Bešlić, Marinka Mravak-Stipetić, Iva Mihatov-Štefanović, Ana-Marija Buntić and Rok Čivljak
Life 2021, 11(9), 962; https://doi.org/10.3390/life11090962 - 14 Sep 2021
Cited by 24 | Viewed by 5759
Abstract
Many relatively common chronic inflammatory skin diseases manifest on the face (seborrheic dermatitis, rosacea, acne, perioral/periorificial dermatitis, periocular dermatitis, etc.), thereby significantly impairing patient appearance and quality of life. Given the yet unexplained pathogenesis and numerous factors involved, these diseases often present therapeutic [...] Read more.
Many relatively common chronic inflammatory skin diseases manifest on the face (seborrheic dermatitis, rosacea, acne, perioral/periorificial dermatitis, periocular dermatitis, etc.), thereby significantly impairing patient appearance and quality of life. Given the yet unexplained pathogenesis and numerous factors involved, these diseases often present therapeutic challenges. The term “microbiome” comprises the totality of microorganisms (microbiota), their genomes, and environmental factors in a particular environment. Changes in human skin microbiota composition and/or functionality are believed to trigger immune dysregulation, and consequently an inflammatory response, thereby playing a potentially significant role in the clinical manifestations and treatment of these diseases. Although cultivation methods have traditionally been used in studies of bacterial microbiome species, a large number of bacterial strains cannot be grown in the laboratory. Since standard culture-dependent methods detect fewer than 1% of all bacterial species, a metagenomic approach could be used to detect bacteria that cannot be cultivated. The skin microbiome exhibits spatial distribution associated with the microenvironment (sebaceous, moist, and dry areas). However, although disturbance of the skin microbiome can lead to a number of pathological conditions and diseases, it is still not clear whether skin diseases result from change in the microbiome or cause such a change. Thus far, the skin microbiome has been studied in atopic dermatitis, seborrheic dermatitis, psoriasis, acne, and rosacea. Studies on the possible association between changes in the microbiome and their association with skin diseases have improved the understanding of disease development, diagnostics, and therapeutics. The identification of the bacterial markers associated with particular inflammatory skin diseases would significantly accelerate the diagnostics and reduce treatment costs. Microbiota research and determination could facilitate the identification of potential causes of skin diseases that cannot be detected by simpler methods, thereby contributing to the design and development of more effective therapies. Full article
(This article belongs to the Special Issue Mechanisms Underlying Skin Pathologies)
14 pages, 730 KiB  
Review
Evolving Mechanisms in the Pathophysiology of Pemphigus Vulgaris: A Review Emphasizing the Role of Desmoglein 3 in Regulating p53 and the Yes-Associated Protein
by Ambreen Rehman, Yunying Huang and Hong Wan
Life 2021, 11(7), 621; https://doi.org/10.3390/life11070621 - 26 Jun 2021
Cited by 8 | Viewed by 4636
Abstract
The immunobullous condition Pemphigus Vulgaris (PV) is caused by autoantibodies targeting the adhesion proteins of desmosomes, leading to blistering in the skin and mucosal membrane. There is still no cure to the disease apart from the use of corticosteroids and immunosuppressive agents. Despite [...] Read more.
The immunobullous condition Pemphigus Vulgaris (PV) is caused by autoantibodies targeting the adhesion proteins of desmosomes, leading to blistering in the skin and mucosal membrane. There is still no cure to the disease apart from the use of corticosteroids and immunosuppressive agents. Despite numerous investigations, the pathological mechanisms of PV are still incompletely understood, though the etiology is thought to be multifactorial. Thus, further understanding of the molecular basis underlying this disease process is vital to develop targeted therapies. Ample studies have highlighted the role of Desmoglein-3 (DSG3) in the initiation of disease as DSG3 serves as a primary target of PV autoantibodies. DSG3 is a pivotal player in mediating outside-in signaling involved in cell junction remodeling, cell proliferation, differentiation, migration or apoptosis, thus validating its biological function in tissue integrity and homeostasis beyond desmosome adhesion. Recent studies have uncovered new activities of DSG3 in regulating p53 and the yes-associated protein (YAP), with the evidence of dysregulation of these pathways demonstrated in PV. The purpose of this review is to summarize the earlier and recent advances highlighting our recent findings related to PV pathogenesis that may pave the way for future research to develop novel specific therapies in curing this disease. Full article
(This article belongs to the Special Issue Mechanisms Underlying Skin Pathologies)
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