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Pathogenesis of Chronic Inflammatory Skin Diseases in the "Omics" Era

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 (30 September 2023) | Viewed by 26077

Special Issue Editors

1. Department of Dermatology, Venereology and Allergology, Medical University of Gdansk, 80-214 Gdansk, Poland
2. Molecular Laboratory, Invicta Fertility and Reproductive Centre, 81-740 Sopot, Poland
Interests: genetic and epigenetic changes in mastocytosis; psoriasis; atopic dermatitis; treg regulation of skin immunology; chemokines and cytokines network in skin diseases; genetic and chromosomal changes in melanomas; sarcomas; T-cell lymphomas and breast carcinomas; genetic and chromosomal causes of infertility; preimplantation, prenatal and postnatal molecular and cytogenetic diagnostic
Special Issues, Collections and Topics in MDPI journals
1. Department of Dermatology, Venerology and Pediatric Dermatology, Medical University of Lublin, 20-081 Lublin, Poland
2. Department of Cosmetology and Aesthetic Medicine, Medical University of Lublin, 20-093 Lublin, Poland
Interests: psoriasis; chronic urticaria; photodynamic therapy; actinic keratosis; skin cancers; cosmetics
Special Issues, Collections and Topics in MDPI journals
Department of Dermatology, Sexually Transmitted Diseases and Clinical Immunology, School of Medicine, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn, Poland
Interests: psoriasis; inflammatory immune-mediated inflammatory disease; metabolic diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Immune-mediated inflammatory diseases (IMIDs) are characterized by dysregulation of the normal immune response, which leads to inflammatory processes. They include systemic lupus erythematosus, rheumatoid arthritis, Crohn’s disease, type 1 diabetes, skin diseases such as psoriasis (Ps), atopic dermatitis (AD), lichen planus (LP), and acne, in addition to neutrophilic diseases. Since the advent of genome-wide association studies (GWAS), there has been evidence of significant overlap in genetics at loci predisposing to a wide range of IMIDs. The genetic grouping largely reflects the response to the used biological therapies. The pathogenesis of these diseases is different, but they have a number of common features: a large genetic component (Ps, AD), stimulation of the skin immune system, and chronic inflammation.

The triggering factors can be classified as either external, e.g., allergens (AD), microorganisms (AD, Ps, acne, LP), drugs (LP, Ps), diet, smoking, and trauma (Ps), or internal, e.g., stress (Ps, AD), autoantigens (Ps, LP), and metabolic disorders (Ps).

Stimulation of the immune system of the skin in both nonspecific response cells (i.e. keratinocytes, dendritic cells (DCs), innate lymphoid type-3 cells (ILC3s), macrophages, mast cells, and neutrophils in the case of Ps; eosinophils, basophils, and innate lymphoid type-2 cells (ILC2s) in the case of AD) and specific response cells (i.e., Th1, Th17, and Th22 lymphocytes in the case of Ps; CD8(+) lymphocytes in Ps and LP; and B lymphocytes as well as CD4+ Th2 in the acute phase and Th1 and Th17 in the chronic phase of AD) causes increased secretion of pro-inflammatory cytokines and chemokines in the skin, an influx of lymphocytes, neutrophils, macrophages, and eosinophils to the skin, and the development of inflammation.

The results of many contemporary published studies have indicated the role of gene mutations/polymorphisms, epistasis, epigenetic gene regulation and regulatory T (Treg) as well as regulatory B (Breg) lymphocyte dysfunction in the etiopathogenesis of these diseases.

Still, little is known about the role of gamma/delta lymphocytes, neutrophils, cytokine and chemokine networks, exosomes, and circulating RNAs in the pathogenesis of IMIDs.

For this Special Issue, supervised by the Guest Editor group and assisted by our Topical Advisory Panel Member Dr. Dorota Purzycka-Bohdan (Medical University of Gdansk), we would like to encourage you to submit reviews and original papers presenting modern knowledge in the field of “omics” (genomics, epigenomics, transcriptomics, proteomics, metabolomics) and the resulting concepts regarding the pathomechanism of selected chronic inflammatory skin diseases and modern methods for personalized treatment with the use of biological drugs.

Dr. Bogusław Nedoszytko
Prof. Dr. Joanna Bartosińska
Prof. Dr. Agnieszka Owczarczyk-Saczonek
Guest Editors

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Keywords

  • chronic inflammatory skin diseases
  • cytokines and chemokines network
  • role of resident and incoming skin cells
  • genomic
  • epigenomic
  • transcriptomic
  • proteomic and metabolomic analysis
  • neurohormones
  • biologic therapy

Published Papers (11 papers)

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Research

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28 pages, 16255 KiB  
Article
Disruptions of Circadian Genes in Cutaneous Melanoma—An In Silico Analysis of Transcriptome Databases
by Monika Lesicka, Bogusław Nedoszytko and Edyta Reszka
Int. J. Mol. Sci. 2023, 24(12), 10140; https://doi.org/10.3390/ijms241210140 - 14 Jun 2023
Cited by 2 | Viewed by 1408
Abstract
Circadian genes are a set of genes that regulate the body’s internal clock and influence various physiological processes, including sleep–wake cycles, metabolism and immune function. Skin cutaneous melanoma (SKCM) is a type of skin cancer that arises from the pigment-producing cells in the [...] Read more.
Circadian genes are a set of genes that regulate the body’s internal clock and influence various physiological processes, including sleep–wake cycles, metabolism and immune function. Skin cutaneous melanoma (SKCM) is a type of skin cancer that arises from the pigment-producing cells in the skin and is the most deadly form of skin cancer. This study has investigated the relevance of circadian gene expression and immune infiltrations in the outcomes of cutaneous melanoma patients. In the present study, in silico methods based on the GEPIa, TIMER 2.0 and cBioPortal databases were performed, so as to investigate the transcript level and prognostic value of 24 circadian genes in SKCM and their relationship with the immune infiltration level. The in silico analysis showed that significantly more than half of the investigated circadian genes have an altered transcript pattern in cutaneous melanoma compared to normal skin. The mRNA levels of TIMELES and BHLHE41 were upregulated, whereas those of NFIL3, BMAL1, HLF, TEF, RORA, RORC, NR1D1, PER1, PER2, PER3, CRY2 and BHLHE40 were downregulated. The presented research shows that SKCM patients with at least one alteration of their circadian genes have decreased overall survival. Additionally, majority of the circadian genes are significantly corelated with the immune cells’ infiltration level. The strongest correlation was found for neutrophils and was followed by circadian genes: NR1D2 r = 0.52 p < 0.0001, BMAL1 r = 0.509 p < 0.0001; CLOCK r = 0.45 p < 0.0001; CSNKA1A1 r = 0.45 p < 0.0001; RORA r = 0.44 p < 0.0001. The infiltration level of immune cells in skin tumors has been associated with patient prognosis and treatment response. Circadian regulation of immune cell infiltration may further contribute to these prognostic and predictive markers. Examining the correlation between circadian rhythm and immune cell infiltration can provide valuable insights into disease progression and guide personalized treatment decisions. Full article
(This article belongs to the Special Issue Pathogenesis of Chronic Inflammatory Skin Diseases in the "Omics" Era)
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19 pages, 903 KiB  
Article
Artificial Intelligence That Predicts Sensitizing Potential of Cosmetic Ingredients with Accuracy Comparable to Animal and In Vitro Tests—How Does the Infotechnomics Compare to Other “Omics” in the Cosmetics Safety Assessment?
by Jadwiga Kalicińska, Barbara Wiśniowska, Sebastian Polak and Radoslaw Spiewak
Int. J. Mol. Sci. 2023, 24(7), 6801; https://doi.org/10.3390/ijms24076801 - 06 Apr 2023
Cited by 1 | Viewed by 2964
Abstract
The aim of the current study was to develop an in silico model to predict the sensitizing potential of cosmetic ingredients based on their physicochemical characteristics and to compare the predictions with historical animal data and results from “omics”-based in vitro studies. An [...] Read more.
The aim of the current study was to develop an in silico model to predict the sensitizing potential of cosmetic ingredients based on their physicochemical characteristics and to compare the predictions with historical animal data and results from “omics”-based in vitro studies. An in silico model was developed with the use of WEKA machine learning software fed with physicochemical and structural descriptors of haptens and trained with data from published epidemiological studies compiled into estimated odds ratio (eOR) and estimated attributable risk (eAR) indices. The outcome classification was compared to the results of animal studies and in vitro tests. Of all the models tested, the best results were obtained for the Naive Bayes classifier trained with 24 physicochemical descriptors and eAR, which yielded an accuracy of 86%, sensitivity of 80%, and specificity of 90%. This model was subsequently used to predict the sensitizing potential of 15 emerging and less-studied haptens, of which 7 were classified as sensitizers: cyclamen aldehyde, N,N-dimethylacrylamide, dimethylthiocarbamyl benzothiazole sulphide, geraniol hydroperoxide, isobornyl acrylate, neral, and prenyl caffeate. The best-performing model (NaiveBayes eAR, 24 parameters), along with an alternative model based on eOR (Random Comittee eOR, 17 parameters), are available for further tests by interested readers. In conclusion, the proposed infotechnomics approach allows for a prediction of the sensitizing potential of cosmetic ingredients (and possibly also other haptens) with accuracy comparable to historical animal tests and in vitro tests used nowadays. In silico models consume little resources, are free of ethical concerns, and can provide results for multiple chemicals almost instantly; therefore, the proposed approach seems useful in the safety assessment of cosmetics. Full article
(This article belongs to the Special Issue Pathogenesis of Chronic Inflammatory Skin Diseases in the "Omics" Era)
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19 pages, 1755 KiB  
Article
Assessment of the Potential Role of Selected Single Nucleotide Polymorphisms (SNPs) of Genes Related to the Functioning of Regulatory T Cells in the Pathogenesis of Psoriasis
by Dorota Purzycka-Bohdan, Bogusław Nedoszytko, Marta Sobalska-Kwapis, Monika Zabłotna, Michał A. Żmijewski, Justyna Wierzbicka, Jolanta Gleń, Dominik Strapagiel, Aneta Szczerkowska-Dobosz and Roman J. Nowicki
Int. J. Mol. Sci. 2023, 24(7), 6061; https://doi.org/10.3390/ijms24076061 - 23 Mar 2023
Cited by 2 | Viewed by 1302
Abstract
Recent studies have indicated a key role of the impaired suppressive capacity of regulatory T cells (Tregs) in psoriasis (PsO) pathogenesis. However, the genetic background of Treg dysfunctions remains unknown. The aim of this study was to evaluate the association of PsO development [...] Read more.
Recent studies have indicated a key role of the impaired suppressive capacity of regulatory T cells (Tregs) in psoriasis (PsO) pathogenesis. However, the genetic background of Treg dysfunctions remains unknown. The aim of this study was to evaluate the association of PsO development with selected single nucleotide polymorphisms (SNPs) of genes in which protein products play a significant role in the regulation of differentiation and function of Tregs. There were three study groups in our research and each consisted of different unrelated patients and controls: 192 PsO patients and 5605 healthy volunteers in the microarray genotyping group, 150 PsO patients and 173 controls in the ARMS–PCR method group, and 6 PsO patients and 6 healthy volunteers in the expression analysis group. The DNA microarrays analysis (283 SNPs of 57 genes) and ARMS–PCR method (8 SNPs in 7 genes) were used to determine the frequency of occurrence of SNPs in selected genes. The mRNA expression of selected genes was determined in skin samples. There were statistically significant differences in the allele frequencies of four SNPs in three genes (TNF, IL12RB2, and IL12B) between early-onset PsO patients and controls. The lowest p-value was observed for rs3093662 (TNF), and the G allele carriers had a 2.73 times higher risk of developing early-onset PsO. Moreover, the study revealed significant differences in the frequency of SNPs and their influence on PsO development between early- and late-onset PsO. Based on the ARMS–PCR method, the association between some polymorphisms of four genes (IL4, IL10, TGFB1, and STAT3) and the risk of developing PsO was noticed. Psoriatic lesions were characterized with a lower mRNA expression of FOXP3, CTLA4, and IL2, and a higher expression of TNF and IL1A in comparison with unaffected skin. In conclusion, the genetic background associated with properly functioning Tregs seems to play a significant role in PsO pathogenesis and could have diagnostic value. Full article
(This article belongs to the Special Issue Pathogenesis of Chronic Inflammatory Skin Diseases in the "Omics" Era)
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10 pages, 422 KiB  
Article
Chemokine Profile in Psoriasis Patients in Correlation with Disease Severity and Pruritus
by Dorota Purzycka-Bohdan, Bogusław Nedoszytko, Monika Zabłotna, Jolanta Gleń, Aneta Szczerkowska-Dobosz and Roman J. Nowicki
Int. J. Mol. Sci. 2022, 23(21), 13330; https://doi.org/10.3390/ijms232113330 - 01 Nov 2022
Cited by 11 | Viewed by 1713
Abstract
Psoriasis (PsO) is a chronic, immune-mediated, inflammatory skin disease associated in most cases with pruritus. Chemokines seem to play a significant role in PsO pathogenesis. The aim of the study was to analyse serum concentrations of CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, CCL5/RANTES, CCL17/TARC, CCL18/PARC, CCL22/MDC [...] Read more.
Psoriasis (PsO) is a chronic, immune-mediated, inflammatory skin disease associated in most cases with pruritus. Chemokines seem to play a significant role in PsO pathogenesis. The aim of the study was to analyse serum concentrations of CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, CCL5/RANTES, CCL17/TARC, CCL18/PARC, CCL22/MDC and CXCL8/IL-8, and their correlation with PsO severity and pruritus intensity. The study included 60 PsO patients and 40 healthy volunteers. Serum concentrations of six (CCL2/MCP-1, CCL3/MIP-1α, CCL5/RANTES, CCL17/TARC, CCL18/PARC and CCL22/MDC) out of eight analysed chemokines were significantly elevated in PsO patients; however, they did not correlate with disease severity. The serum level of CCL5/RANTES was significantly higher in patients with the psoriasis area and severity index (PASI) ≥ 15 (p = 0.01). The serum concentration of CCL17/TARC correlated positively with pruritus assessed using the visual analogue scale (VAS) (R = 0.47; p = 0.05). The study indicated CCL17/TARC as a potential biomarker of pruritus intensity in PsO patients. Chemokines appear to be involved in the development of PsO systemic inflammation. Further detailed studies on the interactions between chemokines, proinflammatory cytokines and immune system cells in PsO are required to search for new targeted therapies. Full article
(This article belongs to the Special Issue Pathogenesis of Chronic Inflammatory Skin Diseases in the "Omics" Era)
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Review

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21 pages, 1180 KiB  
Review
Pathomechanism of Pruritus in Psoriasis and Atopic Dermatitis: Novel Approaches, Similarities and Differences
by Agnieszka Kaczmarska, Dominika Kwiatkowska, Katarzyna Konstancja Skrzypek, Zbigniew Tadeusz Kowalewski, Kamila Jaworecka and Adam Reich
Int. J. Mol. Sci. 2023, 24(19), 14734; https://doi.org/10.3390/ijms241914734 - 29 Sep 2023
Cited by 1 | Viewed by 1322
Abstract
Pruritus is defined as an unpleasant sensation that elicits a desire to scratch. Nearly a third of the world’s population may suffer from pruritus during their lifetime. This symptom is widely observed in numerous inflammatory skin diseases—e.g., approximately 70–90% of patients with psoriasis [...] Read more.
Pruritus is defined as an unpleasant sensation that elicits a desire to scratch. Nearly a third of the world’s population may suffer from pruritus during their lifetime. This symptom is widely observed in numerous inflammatory skin diseases—e.g., approximately 70–90% of patients with psoriasis and almost every patient with atopic dermatitis suffer from pruritus. Although the pathogenesis of atopic dermatitis and psoriasis is different, the complex intricacies between several biochemical mediators, enzymes, and pathways seem to play a crucial role in both conditions. Despite the high prevalence of pruritus in the general population, the pathogenesis of this symptom in various conditions remains elusive. This review aims to summarize current knowledge about the pathogenesis of pruritus in psoriasis and atopic dermatitis. Each molecule involved in the pruritic pathway would merit a separate chapter or even an entire book, however, in the current review we have concentrated on some reports which we found crucial in the understanding of pruritus. However, the pathomechanism of pruritus is an extremely complex and intricate process. Moreover, many of these signaling pathways are currently undergoing detailed analysis or are still unexplained. As a result, it is currently difficult to take an objective view of how far we have come in elucidating the pathogenesis of pruritus in the described diseases. Nevertheless, considerable progress has been made in recent years. Full article
(This article belongs to the Special Issue Pathogenesis of Chronic Inflammatory Skin Diseases in the "Omics" Era)
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25 pages, 391 KiB  
Review
Diseases from the Spectrum of Dermatitis and Eczema: Can “Omics” Sciences Help with Better Systematics and More Accurate Differential Diagnosis?
by Radoslaw Spiewak
Int. J. Mol. Sci. 2023, 24(13), 10468; https://doi.org/10.3390/ijms241310468 - 21 Jun 2023
Cited by 2 | Viewed by 1886
Abstract
Researchers active in the field of inflammatory skin diseases from the spectrum of dermatitis and eczema are well aware of a considerable overlap in the clinical pictures and proposed sets of diagnostic criteria for these diseases, which can hardly be overcome through the [...] Read more.
Researchers active in the field of inflammatory skin diseases from the spectrum of dermatitis and eczema are well aware of a considerable overlap in the clinical pictures and proposed sets of diagnostic criteria for these diseases, which can hardly be overcome through the clinical or epidemiological research. In effect, patients are included in studies based on vague and overlapping criteria, while heterogeneous study populations may, in turn, lead to non-representative outcomes and continued confusion. In this narrative review, a systematics of diseases from the spectrum of dermatitis and eczema is proposed based on the origins of causative factors and the pathomechanisms involved. Difficulties in differentiating between these diseases are discussed, and the extent to which advances in the “omics” sciences might help to overcome them is considered. Of all the “omics” research in this field, more than 90% of the published papers were devoted to atopic dermatitis, with a striking underrepresentation of other diseases from the spectrum of dermatitis and eczema, conditions which collectively exceed the rates of atopic dermatitis by far. A greater “omics” research effort is urgently needed to tackle other dermatitides, like allergic, irritant and protein contact dermatitis, as well as radiation, seborrheic, stasis or autoimmune dermatitis. Atopic dermatitis findings should be validated not only against healthy donors but also other dermatitides. A clinic-oriented approach is proposed for future “omics” studies in the field of dermatitis and eczema. Full article
(This article belongs to the Special Issue Pathogenesis of Chronic Inflammatory Skin Diseases in the "Omics" Era)
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23 pages, 950 KiB  
Review
Proteomic and Metabolomic Changes in Psoriasis Preclinical and Clinical Aspects
by Adrianna Radulska, Iwona Pelikant-Małecka, Kamila Jendernalik, Iwona T. Dobrucki and Leszek Kalinowski
Int. J. Mol. Sci. 2023, 24(11), 9507; https://doi.org/10.3390/ijms24119507 - 30 May 2023
Cited by 3 | Viewed by 1524
Abstract
Skin diseases such as psoriasis (Ps) and psoriatic arthritis (PsA) are immune-mediated inflammatory diseases. Overlap of autoinflammatory and autoimmune conditions hinders diagnoses and identifying personalized patient treatments due to different psoriasis subtypes and the lack of verified biomarkers. Recently, proteomics and metabolomics have [...] Read more.
Skin diseases such as psoriasis (Ps) and psoriatic arthritis (PsA) are immune-mediated inflammatory diseases. Overlap of autoinflammatory and autoimmune conditions hinders diagnoses and identifying personalized patient treatments due to different psoriasis subtypes and the lack of verified biomarkers. Recently, proteomics and metabolomics have been intensively investigated in a broad range of skin diseases with the main purpose of identifying proteins and small molecules involved in the pathogenesis and development of the disease. This review discusses proteomics and metabolomics strategies and their utility in research and clinical practice in psoriasis and psoriasis arthritis. We summarize the studies, from in vivo models conducted on animals through academic research to clinical trials, and highlight their contribution to the discovery of biomarkers and targets for biological drugs. Full article
(This article belongs to the Special Issue Pathogenesis of Chronic Inflammatory Skin Diseases in the "Omics" Era)
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15 pages, 1563 KiB  
Review
Multi-Omics Research Strategies for Psoriasis and Atopic Dermatitis
by Youming Guo, Lingling Luo, Jing Zhu and Chengrang Li
Int. J. Mol. Sci. 2023, 24(9), 8018; https://doi.org/10.3390/ijms24098018 - 28 Apr 2023
Cited by 5 | Viewed by 2231
Abstract
Psoriasis and atopic dermatitis (AD) are multifactorial and heterogeneous inflammatory skin diseases, while years of research have yielded no cure, and the costs associated with caring for people suffering from psoriasis and AD are a huge burden on society. Integrating several omics datasets [...] Read more.
Psoriasis and atopic dermatitis (AD) are multifactorial and heterogeneous inflammatory skin diseases, while years of research have yielded no cure, and the costs associated with caring for people suffering from psoriasis and AD are a huge burden on society. Integrating several omics datasets will enable coordinate-based simultaneous analysis of hundreds of genes, RNAs, chromatins, proteins, and metabolites in particular cells, revealing networks of links between various molecular levels. In this review, we discuss the latest developments in the fields of genomes, transcriptomics, proteomics, and metabolomics and discuss how they were used to identify biomarkers and understand the main pathogenic mechanisms underlying these diseases. Finally, we outline strategies for achieving multi-omics integration and how integrative omics and systems biology can advance our knowledge of, and ability to treat, psoriasis and AD. Full article
(This article belongs to the Special Issue Pathogenesis of Chronic Inflammatory Skin Diseases in the "Omics" Era)
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15 pages, 994 KiB  
Review
Lipid Alterations and Metabolism Disturbances in Selected Inflammatory Skin Diseases
by Julia Nowowiejska, Anna Baran and Iwona Flisiak
Int. J. Mol. Sci. 2023, 24(8), 7053; https://doi.org/10.3390/ijms24087053 - 11 Apr 2023
Cited by 2 | Viewed by 2129
Abstract
Lipidomics is a term used to define the field that analyzes the structure, functions, and interactions of lipids. Inflammatory dermatoses and lipid disturbances are interrelated, especially due to chronic inflammatory conditions. This review discusses lipidomics in selected inflammatory skin diseases: psoriasis, lichen planus, [...] Read more.
Lipidomics is a term used to define the field that analyzes the structure, functions, and interactions of lipids. Inflammatory dermatoses and lipid disturbances are interrelated, especially due to chronic inflammatory conditions. This review discusses lipidomics in selected inflammatory skin diseases: psoriasis, lichen planus, and atopic dermatitis, as well as the less commonly mentioned hidradenitis suppurativa, rosacea, and acne vulgaris. Lipid homeostasis disorders are common; they are especially well-documented in psoriasis, lichen planus, and atopic dermatitis. Future studies are required for better insight into this issue, particularly on the skin lipidome. Understanding lipidomics, in particular skin diseases, increases our knowledge about their pathogenesis, and may become useful in adjusting tailored management for each patient as well establishing prognosis. Noteworthily, it seems advisable to alert doctors to the need to analyze lipid parameters and the complications of abnormal lipid metabolism in dermatological patients, which could decrease their comorbidities and improve the life quality and health condition of dermatological patients. Full article
(This article belongs to the Special Issue Pathogenesis of Chronic Inflammatory Skin Diseases in the "Omics" Era)
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20 pages, 2871 KiB  
Review
The Role of Mast Cells in the Induction and Maintenance of Inflammation in Selected Skin Diseases
by Ewelina Woźniak, Agnieszka Owczarczyk-Saczonek, Magdalena Lange, Justyna Czarny, Ewa Wygonowska, Waldemar Placek and Bogusław Nedoszytko
Int. J. Mol. Sci. 2023, 24(8), 7021; https://doi.org/10.3390/ijms24087021 - 10 Apr 2023
Cited by 8 | Viewed by 2287
Abstract
Under physiological conditions, skin mast cells play an important role as guardians that quickly react to stimuli that disturb homeostasis. These cells efficiently support, fight infection, and heal the injured tissue. The substances secreted by mast cells allow for communication inside the body, [...] Read more.
Under physiological conditions, skin mast cells play an important role as guardians that quickly react to stimuli that disturb homeostasis. These cells efficiently support, fight infection, and heal the injured tissue. The substances secreted by mast cells allow for communication inside the body, including the immune, nervous, and blood systems. Pathologically non-cancerous mast cells participate in allergic processes but also may promote the development of autoinflammatory or neoplastic disease. In this article, we review the current literature regarding the role of mast cells in autoinflammatory, allergic, neoplastic skin disease, as well as the importance of these cells in systemic diseases with a pronounced course with skin symptoms. Full article
(This article belongs to the Special Issue Pathogenesis of Chronic Inflammatory Skin Diseases in the "Omics" Era)
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18 pages, 3649 KiB  
Review
Molecular Mechanisms of Neurogenic Inflammation of the Skin
by Luiza Marek-Jozefowicz, Bogusław Nedoszytko, Małgorzata Grochocka, Michał A. Żmijewski, Rafał Czajkowski, Wiesław J. Cubała and Andrzej T. Slominski
Int. J. Mol. Sci. 2023, 24(5), 5001; https://doi.org/10.3390/ijms24055001 - 05 Mar 2023
Cited by 15 | Viewed by 5270
Abstract
The skin, including the hypodermis, is the largest body organ and is in constant contact with the environment. Neurogenic inflammation is the result of the activity of nerve endings and mediators (neuropeptides secreted by nerve endings in the development of the inflammatory reaction [...] Read more.
The skin, including the hypodermis, is the largest body organ and is in constant contact with the environment. Neurogenic inflammation is the result of the activity of nerve endings and mediators (neuropeptides secreted by nerve endings in the development of the inflammatory reaction in the skin), as well as interactions with other cells such as keratinocytes, Langerhans cells, endothelial cells and mast cells. The activation of TRPV–ion channels results in an increase in calcitonin gene-related peptide (CGRP) and substance P, induces the release of other pro-inflammatory mediators and contributes to the maintenance of cutaneous neurogenic inflammation (CNI) in diseases such as psoriasis, atopic dermatitis, prurigo and rosacea. Immune cells present in the skin (mononuclear cells, dendritic cells and mast cells) also express TRPV1, and their activation directly affects their function. The activation of TRPV1 channels mediates communication between sensory nerve endings and skin immune cells, increasing the release of inflammatory mediators (cytokines and neuropeptides). Understanding the molecular mechanisms underlying the generation, activation and modulation of neuropeptide and neurotransmitter receptors in cutaneous cells can aid in the development of effective treatments for inflammatory skin disorders. Full article
(This article belongs to the Special Issue Pathogenesis of Chronic Inflammatory Skin Diseases in the "Omics" Era)
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