Fibroblasts are mesenchymal cells that constitute the stroma across tissues. Historically, they have long been perceived as uniform structural cells passively residing in the background during the immune responses within tissues. However, a growing number of recent studies have revealed that fibroblasts are highly heterogeneous and dynamic, responding to various external stimuli with notable plasticity. They exhibit heterogeneity not only across tissues but also within the same organ, and show dynamic changes over time throughout development and aging. As a barrier tissue, the skin is constantly exposed to numerous environmental stressors and pathogens and is capable of mounting diverse yet robust immune responses to these stimuli. Reflecting this inherent nature, skin dermal fibroblasts are remarkably heterogeneous and dynamic. Upon tissue inflammation, they produce and secrete not only inflammatory cytokines and chemokines but also extracellular matrix molecules that critically modulate immune cell infiltration. They also engage in direct mechano-chemical interactions with neighboring cells and actively support neural growth. Furthermore, they function as antigen presenting cells and contribute to the formation of tertiary lymphoid structures. This review highlights recent advances in understanding the heterogeneity of dermal fibroblast subpopulations and their roles in the pathogenesis of major inflammatory and autoimmune skin diseases.

Epidermal renewal needs tight control of the cell cycle and proliferation to face the continuous mutagenic pressure of UV light. Cyclin E1 is a key molecule in human epidermis, a main driver of the cell cycle and is frequently deregulated in cancer. Both Cyclin E1 and the homologue Cyclin E2 were shown generally dispensable for normal development and growth. However, their requirement for skin hyperplasia and squamous carcinogenesis was unknown.

Excessive melanogenesis in skin melanocytes results in hyperpigmentation disorders.

Brodalumab, an anti-interleukin-17 receptor A antibody, is effective in psoriasis via action on the IL-17 pathway.

Extramammary Paget's disease (EMPD) occurs in areas where apocrine glands are abundant. EMPD is associated with the known somatic hotspot mutation g.chr14:38064406 G>A in the promoter region of FOXA1 and S310F in ERBB2. Whether EMPD patients in non-Japanese populations have FOXA1 driver mutations remains undetermined, and the relationship between the clinical characteristics of EMPD patients and the presence of somatic FOXA1 driver mutations has yet to be investigated.

In a recent paper, our group described that the presence of double autoreactivity to both LL37 and ADAMTSL5 autoantigens in psoriatic patients decreased the clinical responses to risankizumab, but how this influences the changes in the peripheral inflammatory T-cell populations is still unknown.

Previously, we developed bead aggregation assays with recombinant desmoglein (Dsg) and desmocollin (Dsc) and found that pemphigus autoantibodies directly block the heterophilic trans-interaction of Dsg/Dsc.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder driven by type 2 cytokines, particularly IL-4, IL-13, and IL-31. CD4⁺ Th2 cells have long been considered the primary producers of these cytokines in AD, but the contribution of CD8⁺ Tc2 cells has received limited attention. Recent advances in single-cell RNA sequencing, which allow for cytokine expression profiling at the single-cell level, challenge this traditional paradigm. This review reappraises the cellular sources of IL-13-a key effector cytokine in AD lesions-by not only summarizing prior studies but also reanalyzing multiple publicly available scRNA-seq datasets. These analyses indicate that Tc2 cells may represent a substantial, and in some cases dominant, source of IL-13 in lesional skin, alongside Th2 cells. This perspective invites a reconsideration of the Th2-centric model and proposes that a broader view-including Tc2 cells-is needed to fully understand type 2 immune responses in AD.

Condyloma acuminatum (CA) is caused by low-risk HPV infection and characterized by benign epithelial proliferation. NELL2, as a secreted glycoprotein, is strongly linked to dermatosis, but its function in CA remains unknown.

Melanosome transport is a highly coordinated process involving both microtubule- and actin-dependent mechanisms. Our previous study identified 2-methyl-naphtho[1,2,3-de]quinolin-8-one (MNQO) as an inhibitor of melanosome transport. In the present study, we aimed to elucidate the transcriptional regulation of melanosome transport by identifying the key transcription factors involved in this process.

Rosacea is a common chronic inflammatory skin condition that predominantly affects females, though its underlying mechanisms remain unclear.

Extramammary Paget's disease (EMPD) is a rare cutaneous mucinous adenocarcinoma primarily affect the penoscrotal skin, characterized by the presence of Paget cells scattered within the epidermis. The molecular features of Paget cells remain poorly understood.

Skin aging extends beyond aesthetic concerns and is increasingly recognized as a key contributor to brain aging through neuroendocrine, inflammatory, and neurochemical mechanisms. Traditionally considered as a peripheral barrier, the skin is now recognized as a neuroendocrine organ capable of communicating with the central nervous system (CNS) via hormone secretion, cytokine signaling, and neurotransmitter modulation. Recent literature has begun to formalize the concept of the skin-brain axis as a bidirectional communication system, particularly within the contexts of psychodermatology and neuroimmunology. This review highlights how extrinsic factors such as ultraviolet (UV) radiation and intrinsic aging disrupt skin homeostasis and trigger systemic effects on brain functions. Chronic UV exposure activates the cutaneous hypothalamic-pituitary-adrenal (HPA) axis and increases systemic cortisol levels, impairing hippocampal neurogenesis and cognitive function. UV-induced alterations in neurotransmitters including glutamate, dopamine, and β-endorphins affect learning, memory, and emotion regulation. Importantly, both photoaging and natural skin aging are associated with reduced synthesis of brain-derived neurotrophic factor (BDNF) in the skin, potentially diminishing systemic BDNF availability, and contributing to cognitive decline. Recent studies explored the protective effects of sunscreen and moisturizers in mitigating cutaneous inflammation and reducing neurodegenerative risk. Additionally, topical or dietary interventions, such as plant-derived polyphenols, may restore skin BDNF levels and enhance skin-brain resilience. Collectively, these findings support a paradigm shift: preserving skin health is not only a dermatological goal, but also a promising strategy for mitigating brain aging and promoting cognitive resilience.