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Human umbilical cord Wharton jelly-derived mesenchymal stem cells (hUCMS) might apply to treating chronic autoimmune disorders, as already shown for Sjögren's syndrome, including type 1 diabetes mellitus (T1D). Since naked hUCMS grafts encountered restraints, we enveloped hUCMS, within immunoisolatory microcapsules (CpS-hUCMS), made of our endotoxin-free, clinical grade alginate. We then examined the vitro effects of interferon (IFN)-γ-pretreated CpS-hUCMS on Th17 and Treg of T1D patients (n = 15) and healthy controls (n = 10). Peripheral blood mononuclear cells (PBMCs) were co-cultured with PBMC/CpS-hUCMS: lymphocyte proliferation was assessed by carboxyfluorescein succinimidyl esther (CFSE) dilution assay, and phenotypic analysis of regulatory and effector Tc was also performed. Cytokine expression was performed by bead array and qPCR on IFN-γ-pretreated hUCMS before PBMCs co-culture. CpS-hUCMS restored a correct Treg/Th17 ratio, relevant to the T1D disease process. In summary, we have preliminarily developed a new biohybrid system, associated with immunoregulatory properties, that is ready for in vivo application. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Growing evidence suggests that IL-17-producing T cells, lacking both CD4 and CD8 molecules and defined as double negative (DN) cells, play a pivotal role in the pathogenesis of a number of systemic autoimmune disorders. We recently demonstrated that this T-cell subset is expanded in the peripheral blood (PB) of patients with primary Sjögren's syndrome (pSS), produces IL-17 and accumulates in minor salivary glands (MSGs). We aimed to investigate glandular and PB DN T cells in early pSS in order to verify a possible correlation with MSGs histological patterns and clinical parameters. Methods: Paired samples of PB mononuclear cells and MSGs from pSS patients were evaluated at the diagnosis by flow cytometry and immunofluorescence staining respectively. Histological analysis to identify histological scores, B/T cell segregation and the presence of germinal center (GC)-like structures was also performed. Results: In early stages of pSS, circulating DN T cells appear to be not yet expanded and inversely correlated with circulating CD4+Th17 cells. The number of infiltrating DN T cells were associated with extent of glandular involvement, presence of GC-like structures and dryness symptoms and were inversely correlated with circulating DN T cells. Conclusions: Our findings suggest that DN T cells are actively involved in the pathogenic mechanisms leading to glandular dysfunction and damage in pSS and may play a role in ectopic lymphoneogenesis development occurring during the disease. [Copyright &y& Elsevier]

Objectives The IFN-inducible protein 16 (IFI16) has been detected in sera from patients with autoimmune/inflammatory diseases but not in healthy subjects. This leaking leads to loss of tolerance towards this self-protein and development of autoantibodies. In this study, the clinical significance of both IFI16 protein and anti-IFI16 antibodies (Abs) in rheumatoid arthritis (RA) was investigated. Methods IFI16 protein and anti-IFI16 Abs levels were assessed by ELISA in serum samples from 154 RA patients and 182 healthy controls (HC), and in synovial fluid (SF) samples from 21 RA patients and 25 patients with osteoarthritis (OA). Results Mean serum levels for both IFI16 and anti-IFI16 Abs were higher in RA than in HC with a direct correlation between IFI16 concentration and anti-IFI16 Abs titer. The majority of RA patients with detectable circulating IFI16 protein were also positive for RF/ACPA. The latter group was found positive for anti-IFI16 Abs as well. The mean SF concentrations of both IFI16 protein and anti-IFI16 Abs were higher in RA when compared with control OA. Interestingly, the presence of circulating IFI16 protein, but not anti-IFI16 Abs, significantly correlated with RA-associated pulmonary disease. This correlation was not dependent on the presence of anti-IFI16 Abs, gender and smoking habit. Conclusions Our data demonstrate that the high levels of circulating IFI16 in RA are more frequent in RF/ACPA-positive RA patients and significantly associated with pulmonary involvement. The relevance of circulating IFI16 protein as new clinical biomarker of RA should be verified with additional studies. [ABSTRACT FROM AUTHOR]