Cutaneous barrier leakage and gut inflammation drive skin disease in Omenn syndrome

BACKGROUND: Severe early-onset erythroderma and gut inflammation, with massive tissue infiltration of oligoclonal activated T cells are the hallmark of Omenn syndrome (OS). OBJECTIVE: The impact of altered gut homeostasis in the cutaneous manifestations of OS remains to be clarified. METHODS: We analyzed a cohort of 15 patients with OS and the 129Sv/C57BL/6 knock-in Rag2R229Q/R229Q (Rag2R229Q) mouse model. Homing phenotypes of circulating lymphocytes were analyzed by flow cytometry. Inflammatory cytokines and chemokines were examined in the sera by ELISA and in skin biopsies by immunohistochemistry and in situ RNA hybridization. Experimental colitis was induced in mice by dextran sulfate sodium salt. RESULTS: We show that memory/activated T cells from patients with OS and from the Rag2R229Q mouse model of OS abundantly express the skin homing receptors cutaneous lymphocyte associated antigen and CCR4 (Ccr4), associated with high levels of chemokine C-C motif ligands 17 and 22. Serum levels of LPS are also elevated. A broad Th1/Th2/Th17 inflammatory signature is detected in the periphery and in the skin. Increased Tlr4 expression in the skin of Rag2R229Q mice is associated with enhanced cutaneous inflammation on local and systemic administration of LPS. Likewise, boosting colitis in Rag2R229Q mice results in increased frequency of Ccr4+ splenic T cells and worsening of skin inflammation, as indicated by epidermal thickening, enhanced epithelial cell activation, and dermal infiltration by Th1 effector T cells. CONCLUSIONS: These results support the existence of an interplay between gut and skin that can sustain skin inflammation in OS.status: publishe

Glass production in the Middle Ages from Italy to Central Europe: the contribution of archaeometry to the history of technology

The present paper reports and discusses data obtained by a combined archaeological and archaeometric study carried out on an assemblage of selected Medieval glass finds from the Monastery of St. Severus in Classe (Ravenna, Italy) and ascribable to the 13–16th CE. Glassware belonging to three main typological groups was selected for this study: ampoules, nuppenbecher and kropfflasche. Such a choice mainly stems from the intent to evaluate typological and compositional affinities of these peculiar vessel typologies with the same forms unearthed in different regions of Central Europe, as a starting point for a possible reconstruction of trade contacts between Italy and Central Europe. Archaeological contextualisation of the site and chrono-typological study of glass vessels were associated to ICP-MS (inductively coupled plasma mass spectrometry) and ICP-OES (inductively coupled plasma optical emission spectrometry) analyses, performed to characterise the composition of the glassy matrix (major and minor components as well as trace elements). The results, elaborated according to the archaeometric glass classification and provenancing of raw materials, shed new light on glass production in late Medieval times and can be broaden framed as a starting point for interpreting relations and exchanges between geographical areas and related cultures