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Skin Diseases: From Molecular Mechanisms to Pathology
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Skin Diseases: From Molecular Mechanisms to Pathology

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: 20 June 2025 | Viewed by 5856

Special Issue Editor

Dr. Alessandro Terrinoni

E-Mail Website
Guest Editor
Department of Experimental Medicine, University of Rome “Tor Vergata”, via Montpellier 1, 00133 Rome, Italy
Interests: keratinocyte; skin differentiation; genodermatosis; psoriasis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The skin is a tissue at the interface between the host and the environment. It is the first line of defense against chemicals and physical insults and pathogens. This barrier function is of critical importance, which became evident after injury, in several different types of dermatitis, and in ichthyoses diseases.

Human skin is the largest immune organ that, in addition to providing a strong barrier against external insults, is fundamental in a wide variety of inflammatory processes, including immunity against infections, tumor immunity, autoimmunity, and allergy, continuously exposed to pathogens and external stress. This because, once the barrier is impaired, the rapid but nonspecific innate immune response is recruited in defense, a process that relies on detection of both self and foreign “danger signals” as the initial alarm. Next, the slower, but specific adaptive immune response may be required for definitive clearance of a pathogen.

The number of genetic skin disorders with known genetic defects has increased during the last decade. Advances in molecular biology provide new insights into immune and genetic aspects of skin diseases.

In this Special Issue of IJMS, we will publish cutting-edge information regarding recent advances in the research of skin diseases from molecular viewpoints. We warmly welcome research and review articles concerning a variety of factors relating to skin diseases, including their genetic/epigenetic regulation, therapy, and prevention. In this Special Issue, we aim to present molecular advances in all fields of skin diseases, whether inflammatory, neoplastic, or infectious.

Dr. Alessandro Terrinoni
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • skin diseases
  • immunology
  • genetics

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Published Papers (4 papers)

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Research

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14 pages, 2461 KiB  
Article
Heterogeneous IL-9 Production by Circulating Skin-Tropic and Extracutaneous Memory T Cells in Atopic Dermatitis Patients
by Irene García-Jiménez, Lídia Sans-de San Nicolás, Laia Curto-Barredo, Marta Bertolín-Colilla, Eloi Sensada-López, Ignasi Figueras-Nart, Montserrat Bonfill-Ortí, Antonio Guilabert-Vidal, Anna Ryzhkova, Marta Ferran, Giovanni Damiani, Tali Czarnowicki, Ramon M. Pujol and Luis F. Santamaria-Babí
Int. J. Mol. Sci. 2024, 25(16), 8569; https://doi.org/10.3390/ijms25168569 - 6 Aug 2024
Viewed by 942
Abstract
Interleukin (IL)-9 is present in atopic dermatitis (AD) lesions and is considered to be mainly produced by skin-homing T cells expressing the cutaneous lymphocyte-associated antigen (CLA). However, its induction by AD-associated triggers remains unexplored. Circulating skin-tropic CLA+ and extracutaneous/systemic CLA− memory [...] Read more.
Interleukin (IL)-9 is present in atopic dermatitis (AD) lesions and is considered to be mainly produced by skin-homing T cells expressing the cutaneous lymphocyte-associated antigen (CLA). However, its induction by AD-associated triggers remains unexplored. Circulating skin-tropic CLA+ and extracutaneous/systemic CLA− memory T cells cocultured with autologous lesional epidermal cells from AD patients were activated with house dust mite (HDM) and staphylococcal enterotoxin B (SEB). Levels of AD-related mediators in response to both stimuli were measured in supernatants, and the cytokine response was associated with different clinical characteristics. Both HDM and SEB triggered heterogeneous IL-9 production by CLA+ and CLA− T cells in a clinically homogenous group of AD patients, which enabled patient stratification into IL-9 producers and non-producers, with the former group exhibiting heightened HDM-specific and total IgE levels. Upon allergen exposure, IL-9 production depended on the contribution of epidermal cells and class II-mediated presentation; it was the greatest cytokine produced and correlated with HDM-specific IgE levels, whereas SEB mildly induced its release. This study demonstrates that both skin-tropic and extracutaneous memory T cells produce IL-9 and suggests that the degree of allergen sensitization reflects the varied IL-9 responses in vitro, which may allow for patient stratification in a clinically homogenous population. Full article
(This article belongs to the Special Issue Skin Diseases: From Molecular Mechanisms to Pathology)
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17 pages, 8443 KiB  
Article
Phenylalanine Butyramide: A Butyrate Derivative as a Novel Inhibitor of Tyrosinase
by Ritamaria Di Lorenzo, Vincenzo Di Lorenzo, Teresa Di Serio, Adua Marzocchi, Lucia Ricci, Eleonora Vardaro, Giovanni Greco, Maria Maisto, Lucia Grumetto, Vincenzo Piccolo, Elena Morelli and Sonia Laneri
Int. J. Mol. Sci. 2024, 25(13), 7310; https://doi.org/10.3390/ijms25137310 - 3 Jul 2024
Viewed by 1065
Abstract
Metabolites resulting from the bacterial fermentation of dietary fibers, such as short-chain fatty acids, especially butyrate, play important roles in maintaining gut health and regulating various biological effects in the skin. However, butyrate is underutilized due to its unpleasant odor. To circumvent this [...] Read more.
Metabolites resulting from the bacterial fermentation of dietary fibers, such as short-chain fatty acids, especially butyrate, play important roles in maintaining gut health and regulating various biological effects in the skin. However, butyrate is underutilized due to its unpleasant odor. To circumvent this organoleptic unfavorable property, phenylalanine butyramide (PBA), a butyrate precursor, has been synthesized and is currently available on the market. We evaluated the inhibition of mushroom tyrosinase by butyrate and PBA through in vitro assays, finding IC50 values of 34.7 mM and 120.3 mM, respectively. Docking calculations using a homology model of human tyrosinase identified a putative binding mode of PBA into the catalytic site. The anti-aging and anti-spot efficacy of topical PBA was evaluated in a randomized, double-blind, parallel-arm, placebo-controlled clinical trial involving 43 women affected by photo-damage. The results of this study showed that PBA significantly improved skin conditions compared to the placebo and was well tolerated. Specifically, PBA demonstrated strong skin depigmenting activity on both UV and brown spots (UV: −12.7% and −9.9%, Bs: −20.8% and −17.7% after 15 and 30 days, respectively, p < 0.001). Moreover, PBA brightened and lightened the skin (ITA°: +12% and 13% after 15 and 30 days, respectively, p < 0.001). Finally, PBA significantly improved skin elasticity (Ua/Uf: +12.4% and +32.3% after 15 and 30 days, respectively, p < 0.001) and firmness (Uf: −3.2% and −14.9% after 15 and 30 days, respectively, p < 0.01). Full article
(This article belongs to the Special Issue Skin Diseases: From Molecular Mechanisms to Pathology)
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Review

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18 pages, 1583 KiB  
Review
Combining Phototherapy and Gold-Based Nanomaterials: A Breakthrough in Basal Cell Carcinoma Treatment
by Karolyne Silva Baioco, Raquel Pereira, Tânia Ferreira-Gonçalves, João M. P. Coelho, Maria Manuela Gaspar and Catarina Pinto Reis
Int. J. Mol. Sci. 2024, 25(21), 11494; https://doi.org/10.3390/ijms252111494 - 26 Oct 2024
Viewed by 668
Abstract
Basal cell carcinoma (BCC) is the most common type of skin carcinoma worldwide. BCC development is the result of a complex interaction between environmental, phenotypic, and genetic factors. While conventional treatments such as surgery and topical therapies have demonstrated variable efficacy (some of [...] Read more.
Basal cell carcinoma (BCC) is the most common type of skin carcinoma worldwide. BCC development is the result of a complex interaction between environmental, phenotypic, and genetic factors. While conventional treatments such as surgery and topical therapies have demonstrated variable efficacy (some of them with limited efficacy), they are not free of adverse side effects, most of them debilitating. Thus, there is a notable gap in the literature regarding alternative and non-invasive therapeutic options. This review aims to address this gap, exploring the potential of photothermal therapy (PTT) combined with metallic nanoparticles, namely gold nanoparticles (AuNPs), as a minimally invasive treatment approach. Through a comprehensive review of the literature in the period from 2014 to 2024, using experimental investigations, this review seeks to elucidate the intricate interplay between genetic factors, environmental influences, and the tumor microenvironment in BCC disease progression, with PTT as a potential therapeutic strategy. Those studies confirmed an enhanced targeting of cancer cells and selective ablation of tumor tissue, using emerging technologies like PTT. A significant tumor reduction, often exceeding 50%, was observed, with some studies reporting complete elimination of the tumor. The main adverse effects noted were localized skin irritation and transient hyperpigmentation, but these were generally minimal and manageable, highlighting the promise of PTT as an effective treatment. Thus, by leveraging the unique properties of AuNPs to enhance the effectiveness of PTT, the targeting of cancer cells can more precisely occur, reducing collateral damage to healthy tissues. This approach not only aims to achieve better clinical results, but also contributes to the broader knowledge base in the field of BCC research. Continued research and clinical trials will be crucial in refining those techniques and validating their efficacy, ultimately paving the way for more effective and less invasive treatments for BCC. Full article
(This article belongs to the Special Issue Skin Diseases: From Molecular Mechanisms to Pathology)
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24 pages, 2240 KiB  
Review
Pathogenesis of Inflammation in Skin Disease: From Molecular Mechanisms to Pathology
by Simona N. Shirley, Abigail E. Watson and Nabiha Yusuf
Int. J. Mol. Sci. 2024, 25(18), 10152; https://doi.org/10.3390/ijms251810152 - 21 Sep 2024
Viewed by 2163
Abstract
Many skin diseases begin with inflammatory changes on a molecular level. To develop a more thorough understanding of skin pathology and to identify new targets for therapeutic advancements, molecular mechanisms of inflammation in the context of skin disease should be studied. Current research [...] Read more.
Many skin diseases begin with inflammatory changes on a molecular level. To develop a more thorough understanding of skin pathology and to identify new targets for therapeutic advancements, molecular mechanisms of inflammation in the context of skin disease should be studied. Current research efforts to better understand skin disease have focused on examining the role of molecular processes at several stages of the inflammatory response such as the dysregulation of innate immunity sensors, disruption of both transcriptional and post-transcriptional regulation, and crosstalk between immune and neuronal processes (neuro-immune crosstalk). This review seeks to summarize recent developments in our understanding of inflammatory processes in skin disease and to highlight opportunities for therapeutic advancements. With a focus on publications within the past 5 years (2019–2024), the databases PubMed and EBSCOhost were used to search for peer-reviewed papers regarding inflammatory molecular mechanisms and skin disease. Several themes of research interest regarding inflammatory processes in skin disease were determined through extensive review and were included based on their relative representation in current research and their focus on therapeutic potential. Several skin diseases such as psoriasis, atopic dermatitis, hidradenitis suppurativa, and scleroderma were described in the paper to demonstrate the widespread influence of inflammation in skin disease. Full article
(This article belongs to the Special Issue Skin Diseases: From Molecular Mechanisms to Pathology)
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