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Immunological and Molecular Networks in the Skin and Skin Diseases

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (20 May 2025) | Viewed by 12463

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Special Issue Editor

Dr. Ankit Srivastava

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Guest Editor

1. Department of Dermatology, School of Medicine, Stanford University, Stanford, CA 94305, USA
2. Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 17177 Stockholm, Sweden
Interests: skin; skin inflammation; keratinocytes; non-coding RNAs; miRNA; skin cancers

Special Issue Information

Dear Colleagues,

Human skin is the largest immune organ, continuously exposed to pathogens and external stress. The skin combats infections, regulates body temperature, protects against UV radiation, and maintains immune as well as molecular functions. The skin is an amalgamation of epidermal, dermal, and immune cell niches. The immunological and molecular networks in the skin drive physiological/pathophysiological responses, such as skin homeostasis, skin aging, inflammatory skin diseases, wound healing, and cancers. In the last two–three decades, cutting-edge research has identified novel signaling pathways controlling normal and diseased skin functions. Notably, cellular cross-talk, supported by cytokine/chemokine networks, non-coding RNAs, and signaling proteins, mediates these immune and molecular circuits. This Special Issue highlights the immunological and molecular networks regulating normal and diseased skin.

Dr. Ankit Srivastava
Guest Editor

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Keywords

skin diseases
skin immunology
skin inflammation
skin aging
skin cancers
cytokine/chemokine networks
molecular signaling pathways
non-coding RNAs
targeted therapies

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Published Papers (4 papers)

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Research

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23 pages, 3853 KiB

Open AccessArticle

Keratinocyte-Mediated Antigen Presentation in Psoriasis: Preliminary Insights from In Vitro Studies

by Katarzyna Zima, Dorota Purzycka-Bohdan, Aneta Szczerkowska-Dobosz and Magdalena Gabig-Cimińska

Int. J. Mol. Sci. 2024, 25(24), 13387; https://doi.org/10.3390/ijms252413387 - 13 Dec 2024

Viewed by 1645

Abstract

Antigen presentation plays a critical role in the pathogenesis of immune-mediated disorders. This study aimed to investigate the effects of IFN-γ and a cytokine mix (5MIX: IL-1α, IL-17A, IL-22, OsM, and TNF-α) on the antigen-presenting capabilities of keratinocytes, with a specific focus on immune-mediated dermatological conditions such as psoriasis (Ps). To achieve this, keratinocytes were treated with IFN-γ and 5MIX, and their impact on the expression of key antigen-presentation molecules, HLA-DRα and CD74, was assessed. Transcriptomic analysis revealed that IFN-γ alone altered the expression of 254 genes, highlighting its central role in modulating immune responses, including the recruitment of immune cells and regulation of inflammation. Temporal experiments further demonstrated that IFN-γ and 5MIX enhanced early endocytic activity and lysosomal degradation pathways, both essential for effective antigen presentation and T-cell activation. To extend these findings to a clinical context, a co-culture model using keratinocytes derived from psoriatic patients was established. This model revealed increased cytokine production following antigen stimulation, indicating robust and consistent CD4+ and naïve T-cell responses. These results elucidate the complex dynamics of cytokine signaling and antigen presentation in keratinocytes, providing insights into potential therapeutic strategies for immune-mediated skin disorders like Ps. Full article

(This article belongs to the Special Issue Immunological and Molecular Networks in the Skin and Skin Diseases)

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14 pages, 14007 KiB

Open AccessArticle

H-VISTA Immunohistochemistry Score Is Associated with Advanced Stages in Cutaneous and Ocular Melanoma

by Andreea Cătălina Tinca, Andreea Raluca Szoke, Bianca Andreea Lazar, Emőke Andrea Szász, Alexandru Nicușor Tomuț, Adrian Horațiu Sabău, Iuliu-Gabriel Cocuz, Titiana-Cornelia Cotoi, Raluca Niculescu, Diana Maria Chiorean, Ioana Ancuța Ungureanu, Sabin Gligore Turdean and Ovidiu Simion Cotoi

Int. J. Mol. Sci. 2024, 25(8), 4335; https://doi.org/10.3390/ijms25084335 - 14 Apr 2024

Cited by 1 | Viewed by 3692

Abstract

Melanoma represents a public health issue. One of the biggest goals of current research is to develop new therapeutic options for patients affected by this aggressive tumor. We conducted a retrospective study including 105 patients diagnosed with cutaneous and ocular melanoma, with stages varying from pT1a to pT4b and pT4e, respectively, and we performed immunohistochemistry reactions with the new potential prognostic marker, VISTA (V-domain Ig suppressor of T cell activation). We quantified the expression by applying the H-score adapted for VISTA and divided the patients, based on the median value, into groups that presented high, low, and negative expression. Therefore, we obtained 65 cases with positive expression for cutaneous melanoma and 8 cases with positive expression for ocular melanoma. Forty-one cases presented high expression in cutaneous melanoma and three cases presented high expression in ocular melanoma. In cutaneous melanoma, analytic statistics showed that VISTA expression was associated with a high Breslow index, high mitotic count, high Ki67 expression, and advanced clinicopathological stage. The majority of ocular melanoma cases demonstrating a positive reaction were classified as stage pT3, whereas earlier stages showed a negative reaction. Our findings underscore a significant correlation between VISTA expression and key prognostic factors in melanoma. Looking ahead, the prospect of future randomized studies holds promise in corroborating the clinical relevance of our findings. By further elucidating the intricate relationship between VISTA expression and melanoma progression, new treatment strategies could be found, improving patient outcomes in this challenging neoplasm. Full article

(This article belongs to the Special Issue Immunological and Molecular Networks in the Skin and Skin Diseases)

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Review

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19 pages, 1048 KiB

Open AccessReview

Micro RNA Dysregulation in Keratinocyte Carcinomas: Clinical Evidence, Functional Impact, and Future Directions

by Jessica Conley, Benjamin Genenger, Bruce Ashford and Marie Ranson

Int. J. Mol. Sci. 2024, 25(15), 8493; https://doi.org/10.3390/ijms25158493 - 3 Aug 2024

Viewed by 1651

Abstract

The keratinocyte carcinomas, basal cell carcinoma (BCC), and cutaneous squamous cell carcinoma (cSCC), are the most common cancers in humans. Recently, an increasing body of literature has investigated the role of miRNAs in keratinocyte carcinoma pathogenesis, progression and their use as therapeutic agents and targets, or biomarkers. However, there is very little consistency in the literature regarding the identity of and/or role of individual miRNAs in cSCC (and to a lesser extent BCC) biology. miRNA analyses that combine clinical evidence with experimental elucidation of targets and functional impact provide far more compelling evidence than studies purely based on clinical findings or bioinformatic analyses. In this study, we review the clinical evidence associated with miRNA dysregulation in KCs, assessing the quality of validation evidence provided, identify gaps, and provide recommendations for future studies based on relevant studies that investigated miRNA levels in human cSCC and BCC. Furthermore, we demonstrate how miRNAs contribute to the regulation of a diverse network of cellular functions, and that large-scale changes in tumor cell biology can be attributed to miRNA dysregulation. We highlight the need for further studies investigating the role of miRNAs as communicators between different cell types in the tumor microenvironment. Finally, we explore the clinical benefits of miRNAs as biomarkers of keratinocyte carcinoma prognosis and treatment. Full article

(This article belongs to the Special Issue Immunological and Molecular Networks in the Skin and Skin Diseases)

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14 pages, 599 KiB

Open AccessReview

The Communication from Immune Cells to the Fibroblasts in Keloids: Implications for Immunotherapy

by Xiya Zhang, Xinfeng Wu and Dongqing Li

Int. J. Mol. Sci. 2023, 24(20), 15475; https://doi.org/10.3390/ijms242015475 - 23 Oct 2023

Cited by 10 | Viewed by 4142

Abstract

Keloids are a type of fibrotic disease characterized by excessive collagen production and extracellular matrix (ECM) deposition. The symptoms of pain and itching and frequent recurrence after treatment significantly impact the quality of life and mental health of patients. A deeper understanding of the pathogenesis of keloids is crucial for the development of an effective therapeutic approach. Fibroblasts play a central role in the pathogenesis of keloids by producing large amounts of collagen fibers. Recent evidence indicates that keloids exhibit high immune cell infiltration, and these cells secrete cytokines or growth factors to support keloid fibroblast proliferation. This article provides an update on the knowledge regarding the keloid microenvironment based on recent single-cell sequencing literature. Many inflammatory cells gathered in keloid lesions, such as macrophages, mast cells, and T lymphocytes, indicate that keloids may be an inflammatory skin disease. In this review, we focus on the communication from immune cells to the fibroblasts and the potential of immunotherapy for keloids. We hope that this review will trigger interest in investigating keloids as an inflammatory disease, which may open up new avenues for drug development by targeting immune mediators. Full article

(This article belongs to the Special Issue Immunological and Molecular Networks in the Skin and Skin Diseases)

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