by Denise Lasigliè, Elisabetta Traggiai, Silvia Federici, Maria Alessio, Antonella Buoncompagni, Andrea Accogli, Sabrina Chiesa, Federica Penco, Alberto Martini, Marco Gattorno
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-1ß 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-1ß 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-1ß, 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 and after treatment with IL-1ß blockade. Untreated CAPS patients showed significantly increased IL-17 serum levels as well as a higher frequency of TH17 compared to control subjects. On the contrary, SoJIA patients displayed a frequency of TH17 similar to normal donors, but were found to have significantly increased serum level of IL-6 when compared to CAPS patients or healthy donors. Remarkably, decreased IL-17 serum levels and TH17 frequency were observed in CAPS patients following in vivo IL-1ß blockade. On the same line, MoDCs from CAPS patients exhibited enhanced secretion of IL-1ß and IL-23 upon TLRs stimulation, with a reduction after anti-IL-1 treatment. Conclusion/Significance
These findings further support the central role of IL-1ß in the differentiation of TH17 in human inflammatory conditions.