Mouse models of atopic dermatitis: a critical reappraisal.

Mouse models for atopic dermatitis (AD) are an indispensable preclinical research tool for testing new candidate AD therapeutics and for interrogating AD pathobiology in vivo. In this Viewpoint, we delineate why, unfortunately, none of the currently available so-called "AD" mouse models satisfactorily reflect the clinical complexity of human AD, but imitate more "allergic" or "irriant" contact dermatitis conditions. This limits the predictive value of AD models for clinical outcomes of new tested candidate AD therapeutics and the instructiveness of mouse models for human AD pathophysiology research.

Immune Control by TRAF6-Mediated Pathways of Epithelial Cells in the EIME (Epithelial Immune Microenvironment).

In the protective responses of epithelial tissues, not only immune cells but also non-immune cells directly respond to external agents. Epithelial cells can be involved in the organization of immune responses through two phases. First, the exogenous harmful agents trigger the primary responses of the epithelial cells leading to various types of immune cell activation.

Predictive factors of response to pulse methylprednisolone therapy in patients with alopecia areata: A follow-up study of 105 Japanese patients.

Pulse corticosteroid therapy is effective for alopecia areata (AA) in the early stage. The risk and efficacy of this therapy for patients with several backgrounds, however, remains controversial. To explore the predictive factors of the response and risk factors of this therapy, data from 105 AA patients treated with methylprednisolone (500 mg) i.

The epithelial immune microenvironment (EIME) in atopic dermatitis and psoriasis.

The skin provides both a physical barrier and an immunologic barrier to external threats. The protective machinery of the skin has evolved to provide situation-specific responses to eliminate pathogens and to provide protection against physical dangers. Dysregulation of this machinery can give rise to the initiation and propagation of inflammatory loops in the epithelial microenvironment that result in inflammatory skin diseases in susceptible people.

The immunological anatomy of the skin.

The skin is the outermost organ of the body and is continuously exposed to external pathogens. Upon inflammation, various immune cells pass through, reside in or are recruited to the skin to orchestrate diverse cutaneous immune responses. To achieve this, immune cells interact with each other and even communicate with non-immune cells, including peripheral nerves and the microbiota.

Resolvin E1 attenuates murine psoriatic dermatitis.

The potential of omega-3 poly-unsaturated fatty acids (PUFAs) as a therapeutic target for psoriasis, a chronic inflammatory skin disease of IL-23/IL-17 axis, is a long-disputed question, since various epidemiological studies have suggested the association between high-intake of omega-3 PUFAs and the reduced frequency and severity of psoriasis. However, their actual significance and the molecular mechanisms remain largely unknown. To address these issues, we focused on resolvin E1 (RvE1), an omega-3 PUFAs-derived metabolite, and examined its effects on psoriatic dermatitis, using an imiquimod-induced mouse psoriasis model.

Epithelial TRAF6 drives IL-17-mediated psoriatic inflammation.

Epithelial cells are the first line of defense against external dangers, and contribute to induction of adaptive immunity including Th17 responses. However, it is unclear whether specific epithelial signaling pathways are essential for the development of robust IL-17-mediated immune responses. In mice, the development of psoriatic inflammation induced by imiquimod required keratinocyte TRAF6.

Intravital imaging of cutaneous immune responses.

Various immune cells are present in the skin and modulate the cutaneous immune response. In order to capture such dynamic phenomena, intravital imaging is an important technique and there is a possibility to provide substantial information that is not available using conventional histological analysis. Multiphoton microscope enable direct, three-dimensional, minimally invasive imaging of biological samples with high spatiotemporal resolution, and now become the main method for intravital imaging studies.

Transient elevation of cytoplasmic calcium ion concentration at a single cell level precedes morphological changes of epidermal keratinocytes during cornification.

Epidermal keratinocytes achieve sequential differentiation from basal to granular layers, and undergo a specific programmed cell death, cornification, to form an indispensable barrier of the body. Although elevation of the cytoplasmic calcium ion concentration ([Ca]) is one of the factors predicted to regulate cornification, the dynamics of [Ca] in epidermal keratinocytes is largely unknown. Here using intravital imaging, we captured the dynamics of [Ca] in mouse skin.

Recent advancement in the mechanism of basophil activation.

Basophils have been recognized as crucial players in allergic inflammation. Basophils have the potential to initiate and expand inflammation through the production of specific cytokines and proteases, and are associated with T helper 2 (Th2) immune responses. In addition, recent studies revealed the heterogeneity in basophil populations.

Multipolarity of cytokine axes in the pathogenesis of atopic dermatitis in terms of age, race, species, disease stage and biomarkers.

Atopic dermatitis (AD) is a common T-cell-mediated inflammatory disease of the skin. Signatures of AD are characterized by an impaired skin barrier, aberrant Th2-type cytokine production and intensive pruritus. Transcriptomic analysis, however, has revealed a heterogeneous pathogenesis and the co-existence of multiple cytokine axes of Th17, Th22 and Th1 types, especially in intrinsic (a subtype of AD without skin barrier impairment), pediatric and Asian types of AD.

Biomarkers for evaluation of mast cell and basophil activation.

Mast cells and basophils play a pathogenetic role in allergic, inflammatory, and autoimmune disorders. These cells have different development, anatomical location and life span but share many similarities in mechanisms of activation and type of mediators. Mediators secreted by mast cells and basophils correlate with clinical severity in asthma, chronic urticaria, anaphylaxis, and other diseases.

The etiopathogenesis of atopic dermatitis: barrier disruption, immunological derangement, and pruritus.

Atopic dermatitis (AD) is a common chronic skin inflammatory disorder characterized by recurrent eczema accompanied by an intractable itch that leads to an impaired quality of life. Extensive recent studies have shed light on the multifaceted pathogenesis of the disease. The complex interplay among skin barrier deficiency, immunological derangement, and pruritus contributes to the development, progression, and chronicity of the disease.

Regulation of blood vascular permeability in the skin.

Regulation of blood vessel permeability is essential for the homeostasis of peripheral tissues. This regulation controls the trafficking of plasma contents, including water, vitamins, ions, hormones, cytokines, amyloids, lipoproteins, carrier proteins, and immunoglobulins. The properties of blood vessels vary among tissues based on their structural differences: continuous, fenestrated, or sinusoidal.

Decrease of superficial serine and lactate in the stratum corneum due to repetitive frictional trauma.

Background: Repetitive frictional trauma can be induced in daily and occupational activities, such as daily ablutions with washcloths. The influence of frictional trauma on the skin barrier function, especially in the perspective of the components of stratum corneum (SC), has not yet been studied in detail. Raman spectroscopy is a noninvasive optical technique based on inelastic light scattering that is capable of measuring several components in the skin.

Barrier dysfunction in the skin allergy.

The skin is continuously exposed to external pathogens, and its barrier function is critical for skin homeostasis. Previous studies have shown that the barrier dysfunction is one of the most predisposing factors for the development of skin allergic diseases such as atopic dermatitis. In this article, we summarize how the physical barrier of the skin is organized and review its link to the pathomechanism of skin allergic diseases.