Atopic dermatitis (AD) is a chronic inflammatory skin disease in humans. It was recently noted that the characteristics of epidermal barrier functions critically influence the pathological features of AD. Evidence suggests that claudin-1 (CLDN1), a major component of tight junctions (TJs) in the epidermis, plays a key role in human AD, but the mechanism underlying this role is poorly understood. One of the main challenges in studying CLDN1's effects is that Cldn1 knock-out mice cannot survive beyond 1 d after birth, due to lethal dehydration. Here, we established a series of mouse lines that express Cldn1 at various levels and used these mice to study Cldn1's effects in vivo. Notably, we discovered a dose-dependent effect of Cldn1's expression in orchestrating features of AD. In our experimental model, epithelial barrier functions and morphological changes in the skin varied exponentially with the decrease in Cldn1 expression level. At low Cldn1 expression levels, mice exhibited morphological features of AD and an innate immune response that included neutrophil and macrophage recruitment to the skin. These phenotypes were especially apparent in the infant stages and lessened as the mice became adults, depending on the expression level of Cldn1. Still, these adult mice with improved phenotypes showed an enhanced hapten-induced contact hypersensitivity response compared with WT mice. Furthermore, we revealed a relationship between macrophage recruitment and CLDN1 levels in human AD patients. Our findings collectively suggest that CLDN1 regulates the pathogenesis, severity, and natural course of human AD.claudin-1 | tight junctions | atopic dermatitis

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BackgroundThe momentum to promote physical activity (PA) by various government agencies such as the Japan Sports Agency established in 2015, academic organizations, and companies is increasing towards the Tokyo Olympic and Paralympic Games. The goal of the 2018 Japan Report Card on Physical Activity for Children and Youth is to assess and track levels of health behaviors related to PA in Japanese children and youth, facilitators and barriers for PA, and related health outcomes.MethodsNationally representative data were used to score the indicators.ResultsThe 2018 Japan Report Card on Physical Activity for Children and Youth consists of health behaviors and outcomes (7 indicators), and influences on health behaviors (4 indicators). The key four health behaviors and outcomes (Organized Sport Participation: B—; Active Transportation: A-; Physical fitness: A, Weight status: A) were favorable. Sedentary Behavior received C— grade, while 2 indicators (Overall Physical Activity, and Active Play) could not be graded. In the Influences domain, Family Influence and Community were graded as C—, while School (B+), Community and Environment (B—), and Government Strategies and Investments (B) were favorable.ConclusionsThe 2018 Japan Report Card on Physical Activity for Children and Youth shows that Japanese children and youth have favorable levels of organized sport participation, active transportation to and from school, and physical fitness and weight status. Future nationally representative surveys on overall PA and active play are needed.

The endothelial CXC chemokines, KC and MIP-2, contribute to infiltration of neutrophils in MPO-ANCA-associated vasculitis involving glomerulonephritis. The activation of glomerular endothelial cells by anti-MPO IgG appeared to directly involve a signaling through moesin.