The anti-inflammatory effect of omega 3 polyunsaturated fatty acids has been confirmed in various inflammatory disease models. Maresin-1 (MaR1) is a lipid mediator derived from the omega-3 fatty acid docosahexaenoic acid (DHA) that has displayed strong anti-inflammatory effects in various inflammatory disease models. However, the effect of topical MaR1 on cutaneous inflammation remains unclear. Therefore, we initially examined the anti-inflammatory effects of topical Maresin-1 using an imiquimod (IMQ)-induced psoriasis-like mouse model of inflammation. Topical MaR1 reduced the ear swelling response as seen in histological findings. RT-PCR and flow cytometry analyses revealed MaR1 had no inhibitory effect on IL-23, but MaR1 suppressed IL-17A production by γδTCRmid+ and CD4+ cells in the skin. These inhibitory effects were also observed in a subcutaneous IL-23-injected psoriasis model. MaR1 downmodulated IL-23 receptor (IL-23R) expression by suppressing retinoic acid-related orphan receptor γt (RORγt) expression and internalization in a clathrin-dependent manner in γδTCRmid+ and CD4+ cells. These results lead to assumptions that topical MaR1 may be a new therapeutic agent for psoriasis and other IL-17-mediated cutaneous inflammatory diseases.

Throughout life, it is necessary to adapt to the Earth’s environment in order to survive. A typical example of this is that the daily Earth cycle is different from the circadian rhythm in human beings; however, the ability to adapt to the Earth cycle has contributed to the development of human evolution. In addition, humans can consume and digest Earth-derived foods and use luxury materials for nutrition and enrichment of their lives, as an adaptation to the Earth’s environment. Recent studies have shown that daily lifestyles are closely related to human health; however, less attention has been paid to the fact that obesity due to excessive energy intake, smoking, and alcohol consumption contributes to the development of inflammatory skin diseases. Gluten or wheat protein, smoking and alcohol, sleep disturbance, and obesity drive the helper T (Th)1/Th2/Th17 immune response, whereas dietary fiber and omega-3 fatty acids negatively regulate inflammatory cytokine production. In this review, we have focused on daily lifestyles and the mechanisms involved in the pathogenesis of inflammatory skin diseases.

Cell adhesion ability is one of the components to establish cell organization and shows a great contribution to human body construction consisting of various types of cells mixture to orchestrate tissue specific function. The cell adhesion molecule 1 (CADM1) is a molecule of cell adhesion with multiple functions and has been identified as a tumor suppressor gene. CADM1 has multifunctions on the pathogenesis of malignancies, and other normal cells such as immune cells. However, little is known about the function of CADM1 on cutaneous cells and cutaneous malignancies. CADM1 plays an important role in connecting cells with each other, contacting cells to deliver their signal, and acting as a scaffolding molecule for other immune cells to develop their immune responses. A limited number of studies reveal the contribution of CADM1 on the development of cutaneous malignancies. Solid cutaneous malignancies, such as cutaneous squamous cell carcinoma and malignant melanoma, reduce their CADM1 expression to promote the invasion and metastasis of the tumor. On the contrary to these cutaneous solid tumors except for Merkel cell carcinoma, cutaneous lymphomas, such as adult-T cell leukemia/lymphoma, mycosis fungoides, and Sézary syndrome, increase their CADM1 expression for the development of tumor environment. Based on the role of CADM1 in the etiology of tumor development, the theory of CADM1 contribution will desirably be applied to skin tumors according to other organ malignancies, however, the characteristics of skin as a multicomponent peripheral organ should be kept in mind to conclude their prognoses.

No abstract

Nivolumab was developed as a monoclonal antibody against programmed death receptor-1, an immune checkpoint inhibitor which negatively regulates T-cell proliferation and activation. Intravenous administration of nivolumab was approved for the treatment of unresectable malignant melanoma in 2014 in Japan. When advanced melanoma patients were treated with nivolumab, median overall survival became longer. Overall survival rate was significantly better in nivolumab-treated melanoma patients than dacarbazine-treated melanoma patients. Nivolumab had an acceptable long-term tolerability profile, with 22% of patients experiencing grade 3 or 4 adverse events related to the drug. Therefore, nivolumab can become an alternative therapy for advanced malignant melanoma.