Role of IL-1 beta in the development of human T(H)17 cells: lesson from NLPR3 mutated patients

PLoS One. 2011;6(5):e20014. doi: 10.1371/journal.pone.0020014. Epub 2011 May 26.


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(H)17 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(H)17 compared to control subjects. On the contrary, SoJIA patients displayed a frequency of T(H)17 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(H)17 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(H)17 in human inflammatory conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Arthritis, Juvenile / blood
  • Arthritis, Juvenile / genetics
  • Carrier Proteins / genetics*
  • Child
  • Child, Preschool
  • Cryopyrin-Associated Periodic Syndromes / blood
  • Cryopyrin-Associated Periodic Syndromes / genetics
  • Dendritic Cells / metabolism
  • Dendritic Cells / pathology
  • Female
  • Humans
  • Immunologic Memory
  • Infant
  • Interferon-gamma / metabolism
  • Interleukin-17 / blood
  • Interleukin-1beta / metabolism*
  • Interleukin-23 Subunit p19 / metabolism
  • Interleukin-6 / blood
  • Lymphocyte Count
  • Male
  • Monocytes / cytology
  • Mutation / genetics*
  • NK Cell Lectin-Like Receptor Subfamily B / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Phenotype
  • Receptors, CCR6 / metabolism
  • Th17 Cells / cytology*
  • Th17 Cells / metabolism
  • Young Adult


  • CCR6 protein, human
  • Carrier Proteins
  • IL17A protein, human
  • IL1B protein, human
  • IL23A protein, human
  • IL6 protein, human
  • Interleukin-17
  • Interleukin-1beta
  • Interleukin-23 Subunit p19
  • Interleukin-6
  • KLRB1 protein, human
  • NK Cell Lectin-Like Receptor Subfamily B
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • Receptors, CCR6
  • Interferon-gamma