Role of IL-1 beta in the development of human T H17 cells: Lesson from NLPR3 mutated patients

Denise Lasigliè, Elisabetta Traggiai, Silvia Federici, Maria Alessio, Antonella Buoncompagni, Andrea Accogli, Sabrina Chiesa, Federica Penco, Alberto Martini, Marco Gattorno

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Abstract

Background: T helper 17 cells (T H-17) represent a lineage of effector T cells critical in host defence and autoimmunity. In both mouse and human IL-1β has been indicated as a key cytokine for the commitment to T H-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-1β 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 T H17 cells was quantified upon staphylococcus enterotoxin B (SEB) stimulation. Secretion of IL-1β, 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-1β blockade. Untreated CAPS patients showed significantly increased IL-17 serum levels as well as a higher frequency of T H17 compared to control subjects. On the contrary, SoJIA patients displayed a frequency of T H17 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 T H17 frequency were observed in CAPS patients following in vivo IL-1β blockade. On the same line, MoDCs from CAPS patients exhibited enhanced secretion of IL-1β 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-1β in the differentiation of T H17 in human inflammatory conditions.

Original languageEnglish
Article numbere20014
JournalPLoS One
Volume6
Issue number5
DOIs
Publication statusPublished - 2011

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ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Lasigliè, D., Traggiai, E., Federici, S., Alessio, M., Buoncompagni, A., Accogli, A., Chiesa, S., Penco, F., Martini, A., & Gattorno, M. (2011). Role of IL-1 beta in the development of human T H17 cells: Lesson from NLPR3 mutated patients. PLoS One, 6(5), [e20014]. https://doi.org/10.1371/journal.pone.0020014