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Atopic dermatitis is a chronic inflammatory skin disease with persistent pruritus. To clarify its molecular mechanism, it is important to establish a mouse model similar to the phenotypes of atopic dermatitis patients, particularly in exhibiting scratching behavior. Ikk2, a component of the IκB kinase complex, exerts pro-inflammatory responses, whereas its deficiency in keratinocytes paradoxically causes skin inflammation. In this study, we sought to generate a mouse model exhibiting skin inflammation by which dermal fibroblasts lack Ikk2 expression and evaluate whether cutaneous inflammatory phenotypes are similar to those of atopic dermatitis patients.
Despite extensive discovery about the mutations underlying genetic skin disorders, there have been few therapeutic advances. Better understanding of the molecular changes that may lead to the phenotypic manifestations of genetic disorders may lead to the discovery of new pharmacologic interventions. The ichthyoses are characterized by scaling, inflammation, and an impaired epidermal barrier. Recent studies have uncovered T helper type 17 skewing in ichthyotic skin, resembling psoriasis, and high frequencies of IL-17– and IL-22–expressing T cells in blood, correlating with severity and transepidermal water loss.
Myosin Vb (Myo5b) is an unconventional myosin involved in the actin-dependent transport and tethering of intracellular organelles. In the epidermis, granular keratinocytes accumulate cytoplasmic lamellar bodies (LB), secretory vesicles released at the junction with the stratum corneum which participate actively in the maintenance of the epidermal barrier. We have previously demonstrated that LB biogenesis is controlled by the Rab11a GTPase, known for its ability to recruit the Myo5b motor. In order to better characterize the molecular pathway that controls LB trafficking, we analyzed the role of F-actin and Myo5b in the epidermis.
Psoriasis is a chronic inflammatory autoimmune skin disease that often occurs in rubbed areas undergoing a strong mechanical stretch, such as the elbows and knees. However, the pathologic role of mechanical tension in psoriasis remains unclear. In this study, we investigated the contribution of keratinocyte mechanical stretch to the clinical features of psoriasis. We found that keratinocyte proliferation and skin barrier-associated gene expression increased significantly after 24 h of continuous stretching.
Atopic dermatitis (AD) affects up to 20% of children and adults worldwide. To gain a deeper understanding of the pathophysiology of AD, we conducted a large-scale transcriptomic study of AD with deeply-sequenced RNA-seq samples using long (126) paired-end reads. In addition to the comparisons against previous transcriptomic studies, we conducted in-depth analysis to obtain a high-resolution view of the global architecture of the AD transcriptome and contrasted it with that of psoriasis from the same cohort.
Loss-of-function mutations in the ABCC6 gene cause pseudoxanthoma elasticum (PXE) and type 2 generalized arterial calcification of infancy (GACI), heritable ectopic mineralization disorders without effective treatment. ABCC6 encodes the putative efflux transporter ABCC6 which is predominantly expressed in the liver. While the substrate of ABCC6 remains unknown, recent studies demonstrated that PXE is a metabolic disorder caused by reduced circulating levels of pyrophosphate (PPi), a potent mineralization inhibitor.
Psoriasis is associated with periodontitis, a chronic inflammation of the gingival tissue. However, data about periodontal and dental status of psoriasis patients is sparse. Therefore a prospective study comparing psoriasis patients with controls was conducted.100 psoriasis patients presenting at the outpatients’ service of a specialized Psoriasis-Center and 101 non-psoriatic controls were included in the study. Oral health was assessed using standardized measures including Bleeding on Probing (BOP), Community Periodontal Index (CPI) and dental parameters according to the DMFT-index (cumulative index; teeth registered as decayed (“D”), missing (“M”) and filled (“F”)).
Alex and colleagues explain that GSK2894512 is a topically delivered investigational drug being developed for the treatment of atopic dermatitis and psoriasis. Their aim in this study was to investigate, in a phase I clinical trial, the spatial biodistribution and residency of GSK2894512 within the epidermis and dermis of healthy human participants noninvasively using fluorescence lifetime imaging microscopy (FLIM). The authors concluded that FLIM could be a viable alternative to skin biopsies without the usual patient discomfort and limitations, thereby enabling the direct measurement of skin distribution through longitudinal monitoring.
Although the development of biologic therapies has resulted in major benefits for psoriasis patients, algorithms for prescribing these agents are necessary in light of the associated costs and constrained resources that are available. Information gleaned from revolutionary “omics” fields will likely guide these efforts. However, clinical dermatologists do not yet have these data integrated into daily practice. The UK-based Psoriasis Stratification to Optimise Relevant Therapy (PSORT) initiative aims to develop a stratifier of response prediction for biologics in patients with moderate/severe psoriasis.
Inflammation or nerve injury often results in exaggerated responses to innocuous mechanical stimuli, a condition that is termed mechanical allodynia. Although theories that this pain results from sensitization of peripheral sensory neurons or amplification of the signal at the spinal cord have been proposed, the molecular players involved in this mechanism have remained unclear. In two companion papers, Szczot and colleagues and Murthy and colleagues utilized different mouse models to demonstrate that the mechanosensitive ion channel Piezo2, which is expressed on a variety of somatosensory neurons, mediates sensitivity to mechanical pain in mice.
Editorial note: Welcome to the Journal of Investigative Dermatology (JID) Cells to Surgery Quiz— In this monthly online-only quiz, the first question (“What is your diagnosis?”) relates to the clinical image above, while additional questions concern the findings reported in a JID article by Hamer et al (https://doi.org/10.1016/j.jid.2017.12.037).