Background Barrier disruption and the resulting continuous exposure to allergens are presumed to be responsible for the development of atopic dermatitis (AD). However, the mechanism through which ...skin barrier function is disrupted in patients with AD remains unclear. Objectives Taking into account the fact that the TH 2 milieu impairs keratinocyte terminal differentiation, we sought to clarify our hypothesis that the Janus kinase (JAK)–signal transducer and activator of transcription (STAT) pathway plays a critical role in skin barrier function and can be a therapeutic target for AD. Methods We analyzed the mechanism of keratinocyte differentiation using a microarray and small interfering RNA targeting STATs. We studied the effect of the JAK inhibitor JTE-052 on keratinocyte differentiation using the human skin equivalent model and normal human epidermal keratinocytes. We applied topical JAK inhibitor onto NC/Nga mice, dry skin model mice, and human skin grafted to immunocompromised mice. Results IL-4 and IL-13 downregulated genes involved in keratinocyte differentiation. STAT3 and STAT6 are involved in keratinocyte differentiation and chemokine production by keratinocytes, respectively. Topical application of the JAK inhibitor suppressed STAT3 activation and improved skin barrier function, permitting increases in levels of terminal differentiation proteins, such as filaggrin, and natural moisturizing factors in models of AD and dry skin and in human skin. Conclusion STAT3 signaling is a key element that regulates keratinocyte differentiation. The JAK inhibitor can be a new therapeutic tool for the treatment of disrupted barrier function in patients with AD.
RIPK3 in keratinocytes facilitates psoriatic inflammation by promoting cytokine and chemokine production, independent of the induction of necroptosis. Control of RIPK3 activation may be a novel ...therapeutic target for psoriasis.
Abstract Alopecia areata (AA) is a common and stressful disorder that results in hair loss, and resistant to treatment in some cases. Experimental and clinical evidence suggests that AA is caused by ...autoimmune attack against the hair follicles. The precise pathomechanism, however, remains unknown. Here, we focus on the recent progress in multidisciplinary approaches to the epidemiology, pathogenesis, and new treatments of AA in 996 publications from January 2010 to July 2016, and provide an overview of the current understanding in clinical management and research directions.
Pemphigus is one of such autoantibody-mediated disorders, which is caused by pathogenic autoantibodies against epidermal desmosomal cadherins, desmoglein (Dsg) 1 and Dsg3. Because these ...autoantibodies can directly disrupt epidermal cell-cell adhesion,1 their concentration in the epidermis would be linked to the disease severity. ...we irradiated mouse ears with ultraviolet B and demonstrated a positive correlation of IgG1-MFI with the ultraviolet B irradiation dose (r = 1.00) (Fig 2, C) and with the intensity of skin inflammation as evaluated by ear swelling (r = 0.90) (Fig 2, D). ...to confirm that local inflammation predisposes to the development of the pemphigus phenotype, we used a pathogenic antimouse Dsg3 antibody, AK23. In summary, our results in mice suggest that local inflammation might also enhance anti-Dsg3 antibody deposition in the skin in patients with pemphigus. ...taking skin biopsies from perilesional erythematous (presumably inflammable) areas in autoimmune blistering diseases might be beneficial to increase the DIF sensitivity. NS indicates not significant. 1 M. Amagai, S. Karpati, R. Prussick, V. Klaus-Kovtun, J.R. Stanley, Autoantibodies against the amino-terminal cadherin-like binding domain of pemphigus vulgaris antigen are pathogenic, J Clin Invest, Vol. 90, 1992, 919-926 2 Y. Kano, M. Shimosegawa, Y. Mizukawa, T. Shiohara, Pemphigus foliaceus induced by exposure to sunlight: report of a case and analysis of photochallenge-induced lesions, Dermatology, Vol. 201, 2000, 132-138 3 D.R. Mehregan, R.K. Roenigk, L.E. Gibson, Postsurgical pemphigus, Arch Dermatol, Vol. 128, 1992, 414-415 4 G. Egawa, S. Nakamizo, Y. Natsuaki, H. Doi, Y. Miyachi, K. Kabashima, Intravital analysis of vascular permeability...
Abstract Pemphigus is a life-threatening autoimmune blistering disease. Pemphigus is divided into 4 major types; pemphigus vulgaris, pemphigus foliaceus, paraneoplastic pemphigus, and IgA pemphigus. ...Among them, IgA pemphigus is characterized by tissue-bound and circulating IgA antibodies targeting desmosomal or nondesmosomal cell surface components in the epidermis. Histopathologically, slight epidermal acantholysis and extensive neutrophilic infiltration in either the upper part or all layers of the epidermis were observed. IgA pemphigus is subdivided into intraepidermal neutrophilic IgA dermatosis-type (IEN-type), whose target antigen is still unknown (probably nondesmosomal cell surface protein), and subcorneal pustular dermatosis-type (SPD-type), whose target antigen is desmocollin 1 (Dsc1). We summarize reported cases of IgA pemphigus and describe current knowledge including epidemiology, clinical manifestations, pathology, laboratory tests, pathophysiology, associated diseases, prognosis and treatment, and future perspectives of IgA pemphigus.
Background Brunsting-Perry pemphigoid is a rare subepidermal blistering disease characterized by scarring blisters on the head and neck. However, the identity of the responsible autoantigens is still ...unresolved. Methods We reported a patient with epidermolysis bullosa acquisita who had clinical features typical of Brunsting-Perry pemphigoid and investigated the involved type VII collagen epitopes. The patient was a 65-year-old Japanese woman with a 20-month history of recurrent subepidermal bullae on her head, face, and neck. Results Immunoblot studies revealed that the serum of this patient reacted with type VII collagen, specifically with the noncollagenous domain 1 and the triple-helical domain. The patient responded completely to colchicine monotherapy. Limitations This study was performed on only one case. Conclusion This study suggests that Brunsting-Perry pemphigoid may be a clinical variant of epidermolysis bullosa acquisita.
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