Atopic dermatitis (AD) is a chronic, relapsing immunoinflammatory skin condition characterized by sensations such as pruritis, pain, and neuronal hypersensitivity. The mechanisms underlying these sensations are multifactorial and involve complex crosstalk among several cutaneous components. This review explores the role these components play in the pathophysiology of atopic dermatitis. In the skin intercellular spaces, sensory nerves interact with keratinocytes and immune cells via myriad mediators and receptors. These interactions generate action potentials that transmit pruritis and pain signals from the peripheral nervous system to the brain. Keratinocytes, the most abundant cell type in the epidermis, are key effector cells, triggering crosstalk with immune cells and sensory neurons to elicit pruritis, pain, and inflammation. Filaggrin expression by keratinocytes is reduced in atopic dermatitis, causing a weakened skin barrier and elevated skin pH. Fibroblasts are the main cell type in the dermis and, in atopic dermatitis, appear to reduce keratinocyte differentiation, further weakening the skin barrier. Fibroblasts and mast cells promote inflammation while dermal dendritic cells appear to attenuate inflammation. Inflammatory cytokines and chemokines play a major role in AD pathogenesis. Type 2 immune responses typically generate pruritis, and the type 1 and type 3 responses generate pain. Type 2 responses and increased skin pH contribute to barrier dysfunction and promote dysbiosis of the skin microbiome, causing the proliferation of Staphyloccocus aureus. In conclusion, understanding the dynamic interactions between cutaneous components in AD could drive the development of therapies to improve the quality of life for patients with AD.

Pyoderma gangrenosum (PG) and hidradenitis suppurativa (HS) are stubborn inflammatory skin diseases categorized as neutrophilic hypodermal dermatoses. These conditions exhibit connections with other autoinflammatory disorders driven by immune responses. Their pathogenesis is complex, rooted in significant imbalances in both innate and adaptive immune systems, particularly featuring elevated levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1, IL-8, IL-17, and IL-23. Studies involving skin tissue pathology and serology have indicated that targeting specific cytokines can bring therapeutic benefits. Indeed, many patients in clinical settings have responded positively to such interventions. Yet, given the diverse cytokines in play, focusing on a single one with antibody therapy might not always be effective. When resistance to biologics emerges, a combined approach targeting multiple overactive cytokines with immunosuppressants, for example cyclosporine and Janus kinase inhibitors, could be an option. In the current review, we explore recent therapeutic developments for PG and HS.

Since human skin is the primary interface responding to external mechanical stimuli, extrinsic forces can disrupt its balanced microenvironment and lead to cutaneous lesions. We performed this review to delve into the pathological effects of mechanical pressure on skin from the cellular perspective. Fibroblasts of different subsets act as heterogeneous responders to mechanical load and express diverse functionalities. Keratinocytes relay mechanical signals through mechanosensitive receptors and the ensuing neurochemical cascades to work collaboratively with other cells and molecules in response to pressure. Mast cells release cytokines and neuropeptides, promoting inflammation and facilitating interaction with sensory neurons, while melanocytes can be regulated by pressure through cellular and molecular crosstalk. Adipocytes and stem cells sense pressure to fine-tune their regulations of mechanical homeostasis and cell differentiation. Applying mechanical pressure to the skin can induce various changes in its microenvironment that potentially lead to pathological alterations, such as ischemia, chronic inflammation, proliferation, regeneration, degeneration, necrosis, and impaired differentiation. The heterogeneity of each cellular lineage and subset from different individuals with various underlying skin conditions must be taken into consideration when discussing the pathological effects of pressure on the skin. Thus, elucidating the mechanotransduction and mechanoresponsive pathways from the cellular viewpoint is crucial in diagnosing and managing relevant dermatological disorders.

Psoriasis is a chronic immune-mediated inflammatory skin disease that involves a complex interplay between infiltrated immune cells and keratinocytes. Great progress has been made in the research on the molecular mechanism of coding and non-coding genes, which has helped in clinical treatment. However, our understanding of this complex disease is far from clear. MicroRNAs (miRNAs) are small non-coding RNA molecules that are involved in post-transcriptional regulation, characterised by their role in mediating gene silencing. Recent studies on miRNAs have revealed their important role in the pathogenesis of psoriasis. We reviewed the current advances in the study of miRNAs in psoriasis; the existing research has found that dysregulated miRNAs in psoriasis notably affect keratinocyte proliferation and/or differentiation processes, as well as inflammation progress. In addition, miRNAs also influence the function of immune cells in psoriasis, including CD4+ T cells, dendritic cells, Langerhans cells and so on. In addition, we discuss possible miRNA-based therapy for psoriasis, such as the topical delivery of exogenous miRNAs, miRNA antagonists and miRNA mimics. Our review highlights the potential role of miRNAs in the pathogenesis of psoriasis, and we expect more research progress with miRNAs in the future, which will help us understand this complex skin disease more accurately.

Psoriasis is a chronic inflammatory skin disease characterized by skin infiltration of immune cells and abnormal epidermal thickening. The initial pathogenesis has not been fully elucidated. Non-coding RNAs (ncRNAs), which include long ncRNAs (lncRNAs) and circular RNAs (circRNAs), comprise the majority of genome transcripts and are important influencers of gene transcription and post-transcription modulations. Emerging roles of ncRNAs in psoriasis were identified recently. This review summarizes the existing studies of psoriasis-related lncRNAs and circRNAs. A considerable proportion of the studied lncRNAs and circRNAs regulate keratinocyte mobility, such as keratinocyte proliferation and differentiation. Some lncRNAs and circRNAs are tightly related to keratinocyte inflammation reactions. Other reports demonstrated that they are also implicated in modulating immune cell differentiation, proliferation, and activation. This review might illuminate future psoriasis research and highlight that lncRNAs and circRNAs might act as therapeutic targets.

Cell regenerative therapy is a modern solution for difficult-to-heal wounds. Keratinocytes, the most common cell type in the skin, are difficult to obtain without the creation of another wound. Stem cell differentiation towards keratinocytes is a challenging process, and it is difficult to reproduce in chemically defined media. Nevertheless, a co-culture of keratinocytes with stem cells usually achieves efficient differentiation. This systematic review aims to identify the secretions of normal human keratinocytes reported in the literature and correlate them with the differentiation process. An online search revealed 338 references, of which 100 met the selection criteria. A total of 80 different keratinocyte secretions were reported, which can be grouped mainly into cytokines, growth factors, and antimicrobial peptides. The growth-factor group mostly affects stem cell differentiation into keratinocytes, especially epidermal growth factor and members of the transforming growth factor family. Nevertheless, the reported secretions reflected the nature of the involved studies, as most of them focused on keratinocyte interaction with inflammation. This review highlights the secretory function of keratinocytes, as well as the need for intense investigation to characterize these secretions and evaluate their regenerative capacities.

Psoriasis is a complex chronic inflammatory skin disease caused by the dynamic interplay between multiple genetic risk foci, environmental risk factors, and excessive immunological abnormalities. Psoriasis affects approximately 2% of the population worldwide, and dramatic advances have been achieved in the understanding and treatment options for psoriasis. Recent progress in biological therapies has revealed the fundamental roles of tumor necrosis factor-α, interleukin (IL)-23p19, and the IL-17A axis together with skin-resident immune cells and major signal transduction pathways in the pathogenesis of psoriasis. In addition to IL-17-producing T helper17 cells, innate lymphoid cell (ILC)3 induces psoriasis rashes directly without T-cell/antigen interaction in response to the released antimicrobial peptides from activated keratinocytes and inflammatory cytokines. ILC3 typically expresses retinoic acid receptor-related orphan receptor gamma t in the nucleus, matures in the presence of IL-7 and IL-23, and produces IL-17 and IL-22. The number of ILC3s is increased in the blood, psoriasis rash, and even in nonrash areas of psoriatic skin. Psoriasis is significantly associated with cardiovascular disease, metabolic syndrome, and inflammatory disorders, particularly the severe type. The similarity of enterobacteria in the psoriasis gut to that in diabetic patients may be related to its pathogenesis. In the current review, we focus on the pathophysiology of psoriasis in the accelerated immunological inflammatory loop, danger signal from keratinocytes, and cytokines, particularly IL-17 and IL-23p19. In addition, pathophysiological speculation with regard to morphology has been supplemented. Finally, the differences and similarities between psoriasis and atopic dermatitis are discussed.

Persistent infection with high-risk human papillomaviruses (HR-HPVs) is the causal factor in over 99 % of cervical cancer cases, and a significant proportion of oropharyngeal and anogenital cancers. The key drivers of HPV-mediated transformation are the oncoproteins E5, E6 and E7. Together, they act to prolong cell-cycle progression, delay differentiation and inhibit apoptosis in the host keratinocyte cell in order to generate an environment permissive for viral replication. The oncoproteins also have key roles in mediating evasion of the host immune response, enabling infection to persist. Moreover, prolonged infection within the cellular environment established by the HR-HPV oncoproteins can lead to the acquisition of host genetic mutations, eventually culminating in transformation to malignancy. In this review, we outline the many ways in which the HR-HPV oncoproteins manipulate the host cellular environment, focusing on how these activities can contribute to carcinogenesis.

The skin is an organ with multiple functions, where important inflammatory and immunological processes take place. The integrity of the skin barrier is necessary for it to fulfill its roles. An intact skin barrier requires a physiological keratinization process, but also a normal cutaneous microbial flora. Any change in the proliferation and differentiation of keratinocytes entails the disruption of the skin barrier and the triggering of inflammatory and immunological processes at this level, in response to the aggression of external pathogens. Also, there are several specialised immune cells in the skin (Langerhans cells, T regulator cells, T helper cells), that maintain a balance between pro-inflammatory and anti-inflammatory processes at this level. Disturbing the immune homeostasis causes inflammation and allergic skin reaction. Psoriasis and atopic dermatitis are two inflammatory diseases of the skin, characterized by perturbation of the mechanisms of skin barrier formation. The immune system of the skin is also involved in the pathophysiology of vitiligo and pemphigus. The aim of this review is to offer a brief presentation of the inflammatory and immunological processes that occur in the skin.

Background/Objective: Skin fibrosis is the result of aberrant processes leading to abnormal deposition of extracellular matrix (ECM) in the dermis. In healthy skin, keratinocytes participate to maintain skin homeostasis by actively crosstalking with fibroblasts. Within the wide spectrum of fibrotic skin disorders, relatively little attention has been devoted to the role of keratinocytes for their capacity to participate to skin fibrosis. This systematic review aims at summarizing the available knowledge on the reciprocal interplay of keratinocytes with fibroblasts and their soluble mediators in physiological states, mostly wound healing, and conditions associated with skin fibrosis. Methods: We performed a systematic literature search on PubMed to identify in vitro and ex vivo human studies investigating the keratinocyte characteristics and their interplay with fibroblasts in physiological conditions and within fibrotic skin disorders including hypertrophic scars, keloids, and systemic sclerosis. Studies were selected according to pre-specified eligibility criteria. Data on study methods, models, stimuli and outcomes were retrieved and summarized according to pre-specified criteria. Results: Among the 6,271 abstracts retrieved, 73 articles were included, of which 14 were specifically dealing with fibrotic skin pathologies. Fifty-six studies investigated how keratinocyte may affect fibroblast responses in terms of ECM-related genes or protein production, phenotype modification, and cytokine production. Most studies in both physiological conditions and fibrosis demonstrated that keratinocytes stimulate fibroblasts through the production of interleukin 1, inducing keratinocyte growth factor (KGF) and metalloproteinases in the fibroblasts. When the potential of keratinocytes to modulate collagen synthesis by healthy fibroblasts was explored, the results were controversial. Nevertheless, studies investigating keratinocytes from fibrotic skin, including keloids, hypertrophic scar, and scleroderma, suggested their potential involvement in enhancing ECM deposition. Twenty-three papers investigated keratinocyte proliferation differentiation and production of soluble mediators in response to interactions with fibroblasts. Most studies showed that fibroblasts modulate keratinocyte viability, proliferation, and differentiation. The production of KGF by fibroblast was identified as key for these functions. Conclusions: This review condenses evidence for the active interaction between keratinocytes and fibroblasts in maintaining skin homeostasis and the altered homeostatic interplay between keratinocytes and dermal fibroblasts in scleroderma and scleroderma-like disorders.