title: Role of IL-1 beta in the development of human T(H)17 cells: lesson from NLPR3 mutated patients.
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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  These findings further support the central role of IL-1β in the differentiation of T(H)17 in human inflammatory conditions.
authors.affiliation: Rheumatology Unit, Second Division of Pediatrics G. Gaslini Institute, Genoa, Italy.
authors.forename: Denise
authors.initials: D
authors.lastname: Lasigliè
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Traggiai
authors.forename: Silvia
authors.initials: S
authors.lastname: Federici
authors.forename: Maria
authors.initials: M
authors.lastname: Alessio
authors.forename: Antonella
authors.initials: A
authors.lastname: Buoncompagni
authors.forename: Andrea
authors.initials: A
authors.lastname: Accogli
authors.forename: Sabrina
authors.initials: S
authors.lastname: Chiesa
authors.forename: Federica
authors.initials: F
authors.lastname: Penco
authors.forename: Alberto
authors.initials: A
authors.lastname: Martini
authors.forename: Marco
authors.initials: M
authors.lastname: Gattorno
mesh_terms: D000293:Adolescent; D000328:Adult; D001171:Arthritis, Juvenile / Q000097:blood / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D056587:Cryopyrin-Associated Periodic Syndromes / Q000097:blood / Q000235:genetics; D003713:Dendritic Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D007223:Infant; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000097:blood; D053583:Interleukin-1beta / Q000378:metabolism*; D053760:Interleukin-23 Subunit p19 / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D018655:Lymphocyte Count; D008297:Male; D009000:Monocytes / Q000166:cytology; D009154:Mutation / Q000235:genetics*; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010641:Phenotype; D054399:Receptors, CCR6 / Q000378:metabolism; D058504:Th17 Cells / Q000166:cytology* / Q000378:metabolism; D055815:Young Adult
chemical_list: C106311:CCR6 protein, human; D002352:Carrier Proteins; C508717:IL17A protein, human; C508585:IL1B protein, human; C508840:IL23A protein, human; C508600:IL6 protein, human; D020381:Interleukin-17; D053583:Interleukin-1beta; D053760:Interleukin-23 Subunit p19; D015850:Interleukin-6; C527203:KLRB1 protein, human; D055651:NK Cell Lectin-Like Receptor Subfamily B; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D054399:Receptors, CCR6; D007371:Interferon-gamma