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Background: Acne vulgaris is a disorder of the pilosebaceous unit of the skin, and the underlying mechanism is still obscure. Kyoto rhino (krh/krh) rats were made by ethylnitrosourea (ENU) mutagenesis and harbor S413X nonsense mutation of the rat hairless (Hr) gene. Krh/krh rats develop comedones with hair loss on their back as they grow., Objective: Our purpose is to assess whether or not the krh/krh rat is a suitable model of non-inflammatory acne, and to investigate the comedolytic effects of adapalene in krh/krh rats., Methods: Krh/krh rats at 12weeks of age were topically treated with adapalene or a vehicle 6 times a week, for 12weeks. Skin lesions were clinically investigated and skin samples were obtained from treated skins from each animal after 6 and 12weeks of treatments., Results: Comedone was clinically enlarged in the control group compared with the adapalene group. The adapalene group showed significantly increased epidermal thickness as compared to the control group. Furthermore, open comedone areas were also significantly decreased in the adapalene group as compared to the control group. The adapalene group also showed reduced lipid production in open comedones as compared to the control group. Cytokine productions including IL-10 and IL-12a tended to increase in skin treated with adapalene as compared to the control group., Conclusion: Krh/krh rats represented a new model for non-inflammatory acne with abnormalities in both hair follicles and sebaceous glands. It is hypothesized that adapalene is a superior drug to decrease open comedones by modifying lipid metaboism and cytokine production in krh/krh rats., (Copyright © 2014 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.)

Mouse models are similar but not identical to human diseases. However, they are important for research into the pathogenesis underlying autoimmune diseases because they allow us to evaluate similarities and differences between human diseases and mouse models. In fact, experimental models and inbred lupus-prone mice are tools that enable a better understanding of the 'photosensitivity' or 'photocytotoxicity' phenomena in relation to autoimmunity. Genetic studies of MRL/lpr mice revealed that the appearance of macroscopic lupus erythematosus (LE)-like skin lesions needs the lpr mutation plus an additional factor in an autosomal dominant fashion. The candidate is ultraviolet (UV) B light, the susceptibility to which is regulated by the genetic background. Such a genetic background is also speculated to be important in human cutaneous LE patients. The translocation of anti-SS-A/Ro on cultured keratinocytes irradiated with UVB light is quantitatively different from photocytotoxicity, and the quantitative levels are significantly higher in systemic LE and subacute cutaneous LE than in discoid LE and normal controls. This review focuses on the lessons gleaned from mouse and human models, and discusses photosensitivity in human cutaneous LE.

Sairei-to, one of the Japanese-Chinese herbal medicines has been used for the treatment of various diseases, especially collagen disease and edema in nephrotic syndrome. However, the mechanism of the therapeutic effects remains uncertain. Therefore, we investigated the immunological changes of skin, kidney, spleen cells and serum in autoimmune-prone MRL/lpr, MRL/n and C57BL/6J mice treated with Sairei-to. In MRL/lpr mice treated with Sairei-to, the improvement of proteinuria, reduction in the number of hematoxylin bodies in kidney, and reduced serum levels of blood urea nitrogen were observed. These results indicate that Sairei-to can improve or inhibit the progression of lupus nephritis. The proportion of CD19 and the serum levels of IgG1, which is one of the pathogenesis of lupus dermatoses and lupus nephritis, were significantly reduced in Sairei-to-treated MRL/lpr mice. Therefore, it is suspected that the B cell function was suppressed by Sairei-to. In addition, CD4/8 ratio in spleen cells and the degree of lymphoproliferation in MRL/lpr mice also decreased. Interestingly, IL-4 producing spleen cells were increased significantly by ELISPOT assay, and IFN-gamma mRNA expressions were reduced in Sairei-to-treated MRL/lpr mice. Regarding the Th balance, an imbalance towards Th1 predominance may play a significant role in MRL/lpr mice, and the Th1 axis was suppressed and the Th2 axis became predominant in Sairei-to-treated MRL/lpr mice. On the other hand, Th2 cell type immunoglobulins (IgG1) were suppressed. These results suggested that Sairei-to is potential for impairing shifted Th1/Th2 balance and hypergammaglobulinemia resulting in therapeutic effects.

The immunomodulatory effect of the macrolide antibiotic, roxithromycin (RXM) on Langerhans cells (LC) was studied in mice. RXM inhibited the ability of LC to present superantigen and hapten to T cells at 100 microM. The superantigen-presenting activity of LC was more profoundly abrogated by RXM than the hapten-presenting activity. This functional reduction was partly attributed to an RXM-induced decrease in promotion of the expression of major histocompatibility complex class II molecules on LC. On the other hand, RXM down-modulated the production of interleukin-1 beta by LC at a lower concentration of 10 microM than concentrations that inhibited antigen presentation. These results imply that RXM exerts therapeutic effectiveness via not only bacteriocidal action but also inhibitory effect on the LC ability in T-cell-mediated cutaneous diseases that can be exacerbated by skin-colonized Staphylococcus aureus.