Ocular and Oral Mucous Membrane Pemphigoid (Cicatricial Pemphigoid)

Mucous membrane pemphigoid, a heterogeneous group of autoimmune blistering diseases, affect primarily the mucous membranes. While both oral and ocular mucosae can be affected in a given patient, patients have involvement restricted to oral mucosae tend to have a benign outcome, whereas those with ocular disease commonly face treatment resistance and result in scarring and blindness. Diagnosis requires a direct immunofluorescence microscopy demonstrating a linear deposition of IgG, IgA, or C3 at the epithelial basement membrane. While the target antigens vary, subsets of patients affected exclusively by oral and ocular mucosal diseases have autoantibodies targeting alpha‐6 and beta‐4 integrins, respectively

IL-4 up-regulates epidermal chemotactic, angiogenic, and pro-inflammatory genes and down-regulates antimicrobial genes in vivo and in vitro: Relevant in the pathogenesis of atopic dermatitis

Atopic dermatitis (AD) is a common chronic inflammatory skin disease. Although the pathogenesis of AD is not fully understood, we and others have shown that IL-4 plays a key role. In this study we aimed to identify keratinocyte genes regulated by IL-4 that may play important roles in the pathophysiology of AD. HaCat cells were treated with IL-4 at various concentrations for 24h, and PCR gene array on inflammation/autoimmunity was performed three times for analysis of differential gene expression. Of all the 370 genes examined, 32 and 53 genes are up- and down-regulated, respectively. Specifically related to AD, chemokines CCL3L1, CCL8, CCL24, CCL25, CCL26, CXCL6 and CXCL16 are up-regulated by IL-4. Pro-inflammatory factors, such as IL-19, IL-20, IL-1α, IL-12Rβ2, IL-25, IL-31RA, OSMR and nitric oxide synthase 2, are also up-regulated. In addition, IL-4 up-regulates VEGFA, a pro-angiogenic factor. In contrast, antimicrobial peptides (AMPs) or factors involved in APM production, such as IFN-κ, S100s, Toll-like receptors, and several chemokines are down-regulated. Similarly IL-4 also down-regulates TNF-α, lymphotoxin-β, an IgE suppressor, TNFSF18, a T-cells function regulator, and the glucocorticoid receptor. On the in vivo level, real-time RT-PCR on the selected genes confirmed that IL-4 up-regulates chemokines, proinflammatory cytokines while it suppresses AMP production related genes in the skin obtained from IL-4 Tg mice. Detailed examination of these genes will delineate their specific roles in chemotaxis, inflammation, angiogenesis and AMP production, all of which may contribute to the development and progression of AD

IL-4 dysregulates microRNAs involved in inflammation, angiogenesis and apoptosis in epidermal keratinocytes

IL-4 plays an important role in atopic dermatitis (AD) pathogenesis by dysregulating many key factors at the transcriptional level. In this study, using microRNA array technique and IL-4 transgenic mice, we demonstrated that IL-4 dysregulates microRNAs involved in inflammation, angiogenesis, lymphoangiogenesis and apoptosis. Of all the 372 common microRNAs examined, 26 and 1 microRNAs are up- and down-regulated, respectively. MicroRNA-101-5p, -122-5p, -142-3p, -204-5p, -335-3p, -376a-3p, -378a-5p, -639 and -9-5p are among the most significantly up-regulated microRNAs. MicroRNA-147a, the only down-regulated one in our study, attenuates TLR induced-inflammatory response. These dysregulated microRNAs may provide post-transcriptional regulation of key genes in AD