Cellular and Molecular Mechanisms of Skin Inflammation, Barrier Dysfunction, and Regeneration: From Single-Cell Insights to Natural Product Interventions

The field of skin biology has rapidly evolved with the advent of single-cell and spatial omics, transforming our understanding of skin inflammation, barrier dysfunction, and regeneration. Despite the skin’s critical role as a multifunctional barrier, chronic inflammatory diseases such as atopic dermatitis, psoriasis, and diabetic wounds continue to affect millions worldwide. These disorders are driven by complex interactions among keratinocytes, immune cells, fibroblasts, and neural components, yet conventional therapies often fail to address the underlying cellular heterogeneity and dysregulated signaling pathways. Recent single-cell analyses have uncovered novel cell states, intercellular communication networks, and molecular cascades that govern inflammation and tissue repair. Concurrently, environmental pollutants including heavy metals and plasticizers have emerged as potent disruptors of skin homeostasis. Although growing evidence supports the efficacy of natural products in modulating inflammation and promoting regeneration, their mechanistic bases remain underexplored. An integrative approach combining cellular and molecular insights with natural therapeutics is therefore essential to guide the next generation of skin health interventions.

This Research Topic aims to elucidate the cellular and molecular mechanisms underlying skin inflammation, barrier disruption, and tissue regeneration. Specifically, it seeks to integrate high-resolution single-cell multi-omics with mechanistic studies of natural compounds to uncover how specific cell populations and signaling pathways contribute to disease pathogenesis and recovery. Key questions include how environmental triggers perturb epithelial–immune–fibroblast communication, which molecular targets drive chronic inflammation, and how bioactive natural products restore skin integrity and function. By bridging single-cell systems biology with bioactive compound discovery, this Research Topic aims to advance both basic understanding and therapeutic innovation.

To gather further insights into the molecular and cellular foundations of skin inflammation and regeneration, we welcome articles addressing, but not limited to, the following themes:

o Single-cell multi-omic and spatial analyses of inflammatory skin disorders (e.g., atopic dermatitis, psoriasis, vitiligo, diabetic ulcers, skin cancer).

o Molecular pathways connecting environmental toxicants to skin barrier dysfunction and immune dysregulation.

o Crosstalk among keratinocytes, immune cells, fibroblasts, and sensory neurons in inflammation and repair.

o Mechanistic studies of natural products (polysaccharides, peptides, small molecules) that modulate inflammatory signaling (e.g., JAK2–STAT3, PI3K/AKT/NF-κB).

o Translational models linking cell-state dynamics to diagnostics or therapeutic development.

o Integration of in vitro, in vivo, and patient-derived data for precision skin therapeutics.