Psoriasis is a chronic inflammatory skin disease with numerous involved factors. miR‐146a and miR‐146b (miR‐146a/b) are anti‐inflammatory miRNAs that are increased in psoriatic skin. SERPINB2 has been shown to be upregulated in the inflammation and infections. Here we aimed to study the relationship between miR‐146a/b and SERPINB2 and to delineate the role of SERPINB2 in association of plaque psoriasis. We report increased SERPINB2 expression in the skin of psoriasis patients, which was in a positive relationship with psoriasis severity and in a negative relationship with miR‐146a/b in psoriatic lesions. In cultured keratinocytes, both cellular and secreted SERPINB2 levels were strongly induced in response to IFN‐γ and TNF‐α. Interestingly, SERPINB2 mRNA was downregulated by IL‐17A and the combination of TNF‐α and IL‐17A at time points when miR‐146a was increased. The predicted binding site for miR‐146a/b in 3’ untranslated region of SERPINB2 revealed no activity in luciferase assay, while siRNA silencing of miR‐146a/b direct targets IRAK1 and CARD10 resulted in reduced expression of SERPINB2, suggesting that miR‐146a/b indirectly control SERPINB2 expression in the skin. The siRNA silencing of SERPINB2 increased the expression of IL‐8, CXCL5 and CCL5 and migration of neutrophils revealing its anti‐inflammatory role in keratinocytes. Our data together suggest that SERPINB2 and miR‐146a/b are part of disease‐related network of molecules that are coordinately regulated and act in controlling the inflammatory responses in psoriatic skin.

Vitiligo is a chronic multifactorial depigmentation disorder characterized by the destruction and functional loss of melanocytes. Although a direct cytotoxic T cell attack is thought to be responsible for melanocyte damage, the events leading to the loss of self-tolerance toward melanocytic antigens are not understood. This research aimed to identify novel cellular and molecular factors that participate in vitiligo pathogenesis through the application of gene expression and immunofluorescence analysis of skin biopsy samples along with immunophenotyping of circulating cells. Our study provides insights into the mechanisms involved in melanocyte destruction. The upregulation of stress-ligand MICA/MICB, recognized by activating receptors on innate and innate-like T cells, imply involvement of lymphoid stress surveillance responses in vitiligo lesions. A simultaneous increase in the expression of transcription factor EOMES that is characteristic for innate-like virtual memory T cells, suggest a similar scenario. Local lymphoid stress surveillance has been previously associated with the amplification of systemic humoral responses that were mirrored in our study by increased T follicular helper cells and switched memory B cell proportions in patients with active vitiligo. In addition, microtubule-associated protein light chain 3 staining was compatible with the activation of autophagy in keratinocytes and in the remaining melanocytes of vitiligo lesional skin.

Background: miR-10a-5p has been shown to regulate cancer cell proliferation and invasiveness and endothelial cell inflammatory responses. The function of miR-10a-5p in the skin has not been previously studied. The aim of the current study was to examine miR-10a-5p expression, regulation, and function in keratinocytes (KCs) in association with atopic dermatitis (AD). Methods:The expression of miR-10a-5p and its target genes was analyzed using RT-qPCR, mRNA array analysis, in situ hybridization, and immunofluorescence. The transfection of miRNA mimics, cell cycle distribution analysis, and luciferase assays was used to study miR-10a-5p functions in human primary KCs.Results: miR-10a-5p was found to be upregulated in lesional skin from patients with AD and in proliferating KCs. Array and pathway analysis of IL-1β-stimulated KCs revealed that miR-10a-5p inhibited many genes that affect cell cycle progression and only a few inflammation-related genes. Accordingly, fewer cells in S-phase and reduced proliferation were detected as characteristics of miR-10a-5p-transfected KCs.The influence of miR-10a-5p on cell proliferation was also evident in KCs induced by AD-related cytokines, including IL-4, IL-17, and IL-1β, as measured by the capacity to strongly suppress the expression of the proliferation marker Ki-67. Among AD-related putative direct target genes, we verified hyaluronan synthase 3, a damage-associated positive regulator of KC migration and proliferation, as a direct target of miR-10a-5p. | 2147VAHER Et Al.