role of il-1 beta in the development of human th17 cells lesson from nlpr3 mutated patientsil - 1β在人类th17细胞的发展教训nlpr3突变的病人.pdfVIP

Role of IL-1 Beta in the Development of Human TH17 Cells: Lesson from NLPR3 Mutated Patients ` 1,2 1 1 3 1 Denise Lasiglie , Elisabetta Traggiai , Silvia Federici , Maria Alessio , Antonella Buoncompagni , 1 1 1 2 1 Andrea Accogli , Sabrina Chiesa , Federica Penco , Alberto Martini , Marco Gattorno * 1 Rheumatology Unit, Second Division of Pediatrics ‘‘G. Gaslini’’ Institute, Genoa, Italy, 2 Laboratory of Immunology of Rheumatic diseases, Department of Pediatrics, University of Genoa, Genoa, Italy, 3 Department of Pediatrics, Federico II Hospital, Naples, Italy Abstract Background: T helper 17 cells (TH-17) represent a lineage of effector T cells critical in host defence and autoimmunity. In both mouse and human IL-1b has been indicated as a key cytokine for the commitment to TH-17 cells. Cryopyrin-associated periodic syndromes (CAPS) are a group of inflammatory diseases associated with mutations of the NLRP3 gene encoding the inflammasome component cryopyrin. In this work we asked whether the deregulated secretion of IL-1b secondary to mutations characterizing these patients could affect the IL-23/IL-17 axis. Methodology/Principal Findings: A total of 11 CAPS, 26 systemic onset juvenile idiopathic arthritis (SoJIA) patients and 20 healthy controls were analyzed. Serum levels of IL-17 and IL-6 serum were assessed by ELISA assay. Frequency of TH17 cells was quantified upon staphylococcus enterotoxin B (SEB) stimulation. Secretion of IL-1b, IL-23 and IL-6 by monocyte derived dendritic cells (MoDCs), were quantified by ELISA assay. A total of 8 CAPS and 11 SoJIA patients were also analysed before