RGD Reference Report - Role of IL-1 beta in the development of human T(H)17 cells: lesson from NLPR3 mutated patients. - Rat Genome Database

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

Authors: Lasiglie, D  Traggiai, E  Federici, S  Alessio, M  Buoncompagni, A  Accogli, A  Chiesa, S  Penco, F  Martini, A  Gattorno, M 
Citation: Lasiglie D, etal., PLoS One. 2011;6(5):e20014. doi: 10.1371/journal.pone.0020014. Epub 2011 May 26.
RGD ID: 9068438
Pubmed: (View Article at PubMed) PMID:21637346
DOI: Full-text: DOI:10.1371/journal.pone.0020014

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-1beta 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-1beta 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-1beta, 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-1beta 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-1beta blockade. On the same line, MoDCs from CAPS patients exhibited enhanced secretion of IL-1beta 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-1beta in the differentiation of T(H)17 in human inflammatory conditions.

Annotation

Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Il17a  (interleukin 17A)

Genes (Mus musculus)
Il17a  (interleukin 17A)

Genes (Homo sapiens)
IL17A  (interleukin 17A)


Additional Information