A Newly Identified Spliceosomal Protein AHED is Essential for Homeostasis of the Epidermis.

To identify genes that are essential for the functions of cells and organs, we established a homozygous mutant mouse embryonic stem cell bank from which we identified a gene, named Attenuated Hematopoietic Development (Ahed), that plays an essential role in hematopoiesis. Here, we characterize the role of AHED in the skin by analyzing mice with an epidermis-specific Ahed deficiency. Those mice have apoptotic cells in their epidermis from the perinatal stage.

Lysophospholipase D from Thermocrispum limits psoriatic inflammation by hydrolyzing epidermal lysoplasmalogen produced by group IIF secreted phospholipase A.

Epidermal lipids play important roles in skin homeostasis and diseases. Psoriasis is an inflammatory disease characterized by keratinocyte hyperproliferation and Th17 immune responses. We previously reported that ethanolamine-type lysoplasmalogen (P-LPE), preferentially produced by group IIF secreted PLA (sPLA-IIF/PLA2G2F) that is expressed in the suprabasal epidermis, promotes epidermal hyperplasia in psoriatic inflammation.

Keratinocyte Regnase-1, a Downregulator of Skin Inflammation, Contributes to Protection against Tumor Promotion by Limiting Cyclooxygenase-2 Expression.

We previously showed that the ribonuclease Regnase-1 (Reg1) in keratinocytes plays a role in mitigating skin inflammation by downregulating proinflammatory cytokines. In this study, we explored whether Reg1 also has a protective role against skin carcinogenesis. The chemically induced two-stage carcinogenesis protocol revealed that epidermis-specific Reg1-deficient (Reg1-knockout [Reg1-cKO]) mice developed skin tumors with shorter latency and more multiplicity than control mice.

Use of intralesional blood to determine diffusible biomarkers from skin lesions.

Background: Biomarkers provide beneficial information to make diagnoses and monitor the progression of many skin diseases. However, biomarkers produced by skin lesion may be too low at concentration to be detected in the systemic circulation.

Objective: To address whether intralesional blood (ILB) is advantageous to detect skin-derived biomarkers over circulation blood (CB) of patients with skin diseases.

Oral administration of a novel RORγt antagonist attenuates psoriasis-like skin lesion of two independent mouse models through neutralization of IL-17.

Background: Targeting the IL-17 pathway represents a highly effective strategy for the treatment of psoriasis, using antibodies against IL-17A and IL-17 receptor, suggesting that Th17 cells essentially contribute to development of psoriasis. Th17 differentiation depends on the key transcription factor, RORγt.

Objective: To develop a novel RORγt antagonist which is effective on psoriasis via oral administration.

Psoriatic inflammation facilitates the onset of arthritis in a mouse model.

Psoriatic arthritis (PsA) is a seronegative, inflammatory joint disease associated with psoriasis. In most patients with PsA, skin lesions precede arthritis; however, the causality of skin inflammation for the development of arthritis remains unclear. Gp130F759/F759 knock-in (F759) mice develop autoimmune arthritis after 1 year of age through persistent signal transducer and activator of transcription 3 (Stat3) activation due to impairment in SOCS3-dependent negative regulation.

Barrier abnormality due to ceramide deficiency leads to psoriasiform inflammation in a mouse model.

It has been recognized that ceramides are decreased in the epidermis of patients with psoriasis and atopic dermatitis. Here, we generated Sptlc2 (serine palmitoyltransferase long-chain base subunit 2)-targeted mice (SPT-cKO mice), thereby knocking out serine palmitoyltransferase (SPT), the critical enzyme for ceramide biosynthesis, in keratinocytes. SPT-cKO mice showed decreased ceramide levels in the epidermis, which impaired water-holding capacity and barrier function.