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Molecular Pathways, Microbiome, and Chronic Inflammatory Skin Diseases: Bridging the...
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Molecular Pathways, Microbiome, and Chronic Inflammatory Skin Diseases: Bridging the Gap

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

Deadline for manuscript submissions: closed (20 May 2026) | Viewed by 6273

Editor

Dr. Oliver Seifert

E-Mail Website
Guest Editor
Department of Biomedical and Clinical Sciences (BKV), Linköpings Universitet, Linkoping, Sweden
Interests: microbiome; psoriasis; chronic skin diseases; autoimmune bullous diseases; keloid scarring

Special Issue Information

Dear Colleagues,

This Special Issue will explore the molecular keystones of psoriasis and other chronic inflammatory skin diseases, with a particular focus on the interaction between the skin microbiome and host immune responses. Advances in genomics, transcriptomics, proteomics, and metabolomics have provided novel insights into the pathogenesis of conditions such as psoriasis, atopic dermatitis, and autoimmune bullous dermatoses. We welcome original research and reviews that investigate molecular signaling pathways, cytokine networks, microbe–host interactions, and skin barrier dysfunction. Studies addressing the impact of microbiome composition on immune activation, therapeutic response, and disease progression are of particular interest. We also encourage submissions applying systems biology approaches or identifying molecular biomarkers for diagnosis, prognosis, or targeted therapy. By highlighting these molecular-level insights, this Special Issue will deepen our understanding of chronic dermatoses and pave the way for precision medicine in dermatology.

Dr. Oliver Seifert
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 250 words) can be sent to the Editorial Office for assessment.

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-anonymized 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

  • psoriasis
  • skin microbiome
  • chronic inflammatory skin diseases
  • molecular pathogenesis
  • biomarkers

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Published Papers (2 papers)

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Research

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16 pages, 3599 KB  
Article
Integrated Host Genetics and Skin Microbiome Profiling Suggest an HLA-C–Peptostreptococcus Axis in Psoriasis
by Oliver Seifert, Malin Assarsson, Lokeshwaran Manoharan and Jan Söderman
Int. J. Mol. Sci. 2026, 27(9), 4116; https://doi.org/10.3390/ijms27094116 - 4 May 2026
Viewed by 437
Abstract
Psoriasis is a chronic immune-mediated disease driven by genetic susceptibility and environmental factors, including microbial exposure. While HLA-C-linked variants represent the strongest genetic risk factors, their relationship with the cutaneous microbiome remains incompletely understood. This study aimed to investigate host–microbiome interactions in psoriasis [...] Read more.
Psoriasis is a chronic immune-mediated disease driven by genetic susceptibility and environmental factors, including microbial exposure. While HLA-C-linked variants represent the strongest genetic risk factors, their relationship with the cutaneous microbiome remains incompletely understood. This study aimed to investigate host–microbiome interactions in psoriasis through integrative multi-omics analysis. Skin microbiome profiling using 16S rRNA sequencing and targeted genotyping of psoriasis-associated single-nucleotide polymorphisms (SNPs) was performed in lesional and non-lesional skin from patients with plaque psoriasis and in healthy controls. Integrated analysis was conducted using supervised multivariate modeling (DIABLO) to identify coordinated genetic and microbial features associated with disease status. Combined genetic and microbial signatures differentiated lesional, non-lesional, and healthy skin. Variants within the HLA-C susceptibility region, including rs12191877, rs10484554, and rs4406273, showed contributions to group separation and demonstrated positive associations with Peptostreptococcus anaerobius. Associations involving ERAP1 variants linked antigen-processing pathways with inflammation-associated microbial taxa in lesional skin. Importantly, genotype–microbiome correlations were also detected in clinically non-lesional skin, where an increased psoriasis risk allele dosage co-varied with a higher relative abundance of P. anaerobius and Aerococcus urinae. In contrast, commensal-associated taxa were enriched in healthy controls and formed genotype-linked clusters only in non-lesional skin. These findings suggest that psoriasis is characterized by coordinated host genetic and microbial interaction patterns centered on antigen presentation pathways. The presence of a genotype–microbiome coupling in non-lesional skin may indicate that genetically determined immune configurations could shape microbial community structure prior to visible lesion development. Rather than reflecting uniform dysbiosis, psoriasis may represent a dynamic host–microbe ecosystem in which genetic susceptibility influences microbial persistence and inflammatory readiness. Full article
(This article belongs to the Special Issue Molecular Pathways, Microbiome, and Chronic Inflammatory Skin Diseases: Bridging the Gap)
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Review

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12 pages, 238 KB  
Review
Topical Ruxolitinib and Delgocitinib Versus Systemic JAK Inhibitors: A Comparative Safety Review
by Simone Lisa Böll, Seyed Morteza Seyed Jafari, Curdin Conrad and Christoph Schlapbach
Int. J. Mol. Sci. 2025, 26(21), 10592; https://doi.org/10.3390/ijms262110592 - 30 Oct 2025
Cited by 6 | Viewed by 5389
Abstract
Janus Kinase Inhibitors (JAKi) represent a novel class of drugs for the treatment of chronic inflammatory skin diseases. Topical JAKi (t-JAKi) offer targeted therapy at potentially reduced systemic side effects and improved long-term safety compared to systemic JAKi (s-JAKi). This narrative review assesses [...] Read more.
Janus Kinase Inhibitors (JAKi) represent a novel class of drugs for the treatment of chronic inflammatory skin diseases. Topical JAKi (t-JAKi) offer targeted therapy at potentially reduced systemic side effects and improved long-term safety compared to systemic JAKi (s-JAKi). This narrative review assesses the pharmacokinetics and safety profile of currently available t-JAKi, ruxolitinib and delgocitinib, with a comparative analysis to s-JAKi. Pharmacokinetic data show that topical ruxolitinib achieves effective dermal concentrations, with minimal systemic exposure. Clinical trials consistently report low rates of adverse events, primarily application-site reactions, while systemic events such as upper respiratory tract infections occur at rates comparable to placebo. Data on delgocitinib similarly indicate negligible systemic absorption and a favorable safety profile. Taken together, these findings suggest that t-JAKi may represent safer alternatives to s-JAKi for selected patients with localized inflammatory skin diseases, particularly those with comorbidities or heightened systemic risk. Long-term studies and real-world evidence are needed to confirm sustained safety and guide their optimal integration into clinical practice. Full article
(This article belongs to the Special Issue Molecular Pathways, Microbiome, and Chronic Inflammatory Skin Diseases: Bridging the Gap)
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