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Background The thymus plays an essential role in removing autoreactive T cells. Autoantigen-expressing thymic epithelial cells (TECs) contribute to the tolerogenic process. The thymus transiently shrinks as an acute thymic involution (ATI) under various inflammatory conditions. However, whether ATI occurs during local skin inflammation remains unclear, as does its influence on thymic immune tolerance. Objective We investigated whether imiquimod-induced dermatitis causes ATI and impairs thymic immune tolerance against desmoglein 3 (Dsg3), an epidermal autoantigen of pemphigus vulgaris. Methods 5% imiquimod cream was applied daily, at 62.5 mg/day (high dose group) or 31.25 mg/day (low dose group), for 1 week on the back of wild-type mice, and to wild-type mice that had undergone bone-marrow transplantation from Dsg3-specific T-cell receptor (TCR) transgenic-Rag2−/− mice. Next, thymocytes, TECs and other immune cells were analyzed by flow cytometry. TEC-associated Dsg3 expression was also analyzed by immunofluorescence staining. Results Thymus weight and thymocyte number in all developmental stages decreased in a dose-dependent manner under imiquimod-induced dermatitis. The number of total TECs, specifically medullary, but not cortical, TECs, decreased in high and low dose groups. Accordingly, the number of Dsg3-experssing UEA-1+keratin 5+mTEC decreased in the thymus during imiquimod-induced dermatitis. Although Dsg3-sepcific transgenic thymocytes was usually deleted in the thymus under physiological condition by central tolerance, Dsg3-sepcific transgenic CD4+CD8− thymocytes significantly increased in number under imiquimod-induced dermatitis. Conclusion These findings indicate a crosstalk between skin and thymus in adult mice and suggest that skin inflammation may impair thymic tolerance to autoantigens, such as Dsg3.

Nail patella syndrome is a autosomal dominant disorder caused by a genetic alteration in LMX1B. We identified a novel heterozygous in-frame indel mutation of LMX1B in a family of Nail patella syndrome. Impaired transcriptional activity but not dominant negative effect of mutant LMX1B were revealed using a transcriptional reporter assay, indicating that the mutation caused nail patella syndrome in this family via haploinsufficiency of the transcriptional activity of LMX1B.

The pathological mechanisms and immunological kinetics of drug-induced hypersensitivity syndrome (DIHS), including the relevance of interleukin (IL)-6, remain unclear. We report a case of drug adverse reaction that does not fulfill the diagnostic criteria of DIHS but mimics its characteristic features. Because the patient was under anti-IL-6 therapy at the onset, some symptoms typically seen in DIHS were absent, such as fever and leukocyte count abnormalities. However, the characteristic features of DIHS were clearly observed in the subsequent course, including the repeated recurrence of skin rash, prolonged liver dysfunction and reactivation of herpes viruses. This case suggested that IL-6 role at the onset is not a main factor to determine the subsequent pathomechanism of DIHS and attention should be paid to the preceding therapy for achieving accurate diagnosis.

Both acquired perforating dermatosis (APD) and bullous pemphigoid (BP) are associated with a wide variety of systemic and cutaneous disorders [1, 2]. However, coexistence of APD and BP has never been reported. Herein, we describe three patients with coexisting BP and APD. The patients had several common features, suggesting that this condition is a new and unique clinical presentation associated with BP.Patient 1 was a 65-year-old male who presented with a three-month history of pruritic skin lesions [...]

Summary Background Giant congenital nevocellular nevi (GCNN) are histologically characterized by the broad distribution of nevus cells in the epidermis and dermis. Objective To characterize E-cadherin in GCNN and define its role in nevic cell migrations. Methods Twenty-four cases were immunohistochemically examined and in five cases cells were isolated for primary culture for migration assays. Results The nevus cells in the superficial region showed the immunoreactivity of E-cadherin in a membranous pattern, but those in the deep part of dermis had little immunoreactivity. Ultra-structural analysis of the superficial nevus cells revealed that E-cadherin immunodeposits in the fibrillar processes around the cell body in a spotted pattern. This distribution pattern is quite different from that in the adherens junction of skin squamous epithelial cells. Boyden chamber experiments were performed using primary cultures of intradermal nevus cells. EDTA pretreatment reduced cell migration to the E-cadherin positive side when the E-cadherin positive population was relatively large in the primary cultures. Conclusions These results indicate that E-cadherin in the nevus cells may affect nevus cell motility rather than intercellular attachment.