The skin barrier is broadly composed of two elements—a physical barrier mostly localised in the epidermis, and an immune barrier localised in both the dermis and epidermis. These two systems interact cooperatively to maintain skin homeostasis and overall human health. However, if dysregulated, several skin diseases may arise. Psoriasis is one of the most prevalent skin diseases associated with disrupted barrier function. It is characterised by the formation of psoriatic lesions, the aberrant differentiation and proliferation of keratinocytes, and excessive inflammation. In this review, we summarize recent discoveries in disease pathogenesis, including the contribution of keratinocytes, immune cells, genetic and environmental factors, and how they advance current and future treatments.

Independent of its well-known anticoagulation effects, activated protein C (APC) exhibits pleiotropic cytoprotective properties. These include anti-inflammatory actions, anti-apoptosis, and endothelial and epithelial barrier stabilisation. Such beneficial effects have made APC an attractive target of research in a plethora of physiological and pathophysiological processes. Of note, the past decade or so has seen the emergence of its roles in cutaneous wound healing—a complex process involving inflammation, proliferation and remodelling. This review will highlight APC’s functions and mechanisms, and detail its pre-clinical and clinical studies on cutaneous wound healing.

Objectives Endothelial protein C receptor (EPCR) is highly expressed in synovial tissues of patients with rheumatoid arthritis (RA), but the function of this receptor remains unknown in RA. This study investigated the effect of EPCR on the onset and development of inflammatory arthritis and its underlying mechanisms. Methods Collagen-induced arthritis (CIA) was induced in EPCR gene knockout (KO) and matched wild type (WT) mice. The onset and development of arthritis was monitored clinically and histologically. T cells, dendritic cells (DCs), EPCR and cytokines from EPCRKO and WT mice, RA patients and healthy controls (HC) were detected by flow cytometry and ELISA. Results EPCRKO mice displayed >40% lower arthritis incidence and 50% less disease severity than WT. EPCRKO mice also had significantly less Th1/Th17 cells in synovial tissues with more DCs in circulation. Lymph nodes and synovial CD4 T cells from EPCRKO mice expressed less chemokine receptors CXCR3, CXCR5 and CCR6 than WT. In vitro, EPCRKO spleen cells contained less Th1 and more Th2 and Th17 cells than WT, and, in concordance, blocking EPCR in WT cells stimulated Th2 and Th17 cells. DCs generated from EPCRKO bone marrow were less mature and produced less matrix metalloproteinase-9. Circulating T cells from RA patients expressed higher levels of EPCR than HC cells; blocking EPCR stimulated Th2 and Treg cells in vitro. Conclusion Deficiency of EPCR ameliorates arthritis in CIA via inhibition of the activation and migration of pathogenic Th cells and DCs. Targeting EPCR may constitute a novel strategy for future RA treatment.