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

Lasigliè D, Traggiai E, Federici S, Alessio M, Buoncompagni A, Accogli A, Chiesa S, Penco F, Martini A, Gattorno M - PLoS ONE (2011)

Bottom Line: T helper 17 cells (T(H)-17) represent a lineage of effector T cells critical in host defence and autoimmunity.Secretion of IL-1β, IL-23 and IL-6 by monocyte derived dendritic cells (MoDCs), were quantified by ELISA assay.These findings further support the central role of IL-1β in the differentiation of T(H)17 in human inflammatory conditions.

View Article: PubMed Central - PubMed

Affiliation: Rheumatology Unit, Second Division of Pediatrics G. Gaslini Institute, Genoa, Italy.

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(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.

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Related in: MedlinePlus

elevated level of IL-1β and IL-23 secreted by MoDCs of CAPS patients upon Zymosan stimulation.Secretion of IL-1β (A), IL-23 (B) and IL-6 (C) by MoDs upon 48 hours of challenge with or without Zymosan in 4 CAPS patients, 10 healthy controls and 4 active SoJIA patients. Bold horizontal lines represent median values. Boxes contain the 50% of values falling between the 25th and 75th percentiles, whiskers lines that extend from the boxes represent the highest and lowest values for each subgroups. Statistical analysis was performed using non-parametric U Mann-Whitney test.
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pone-0020014-g004: elevated level of IL-1β and IL-23 secreted by MoDCs of CAPS patients upon Zymosan stimulation.Secretion of IL-1β (A), IL-23 (B) and IL-6 (C) by MoDs upon 48 hours of challenge with or without Zymosan in 4 CAPS patients, 10 healthy controls and 4 active SoJIA patients. Bold horizontal lines represent median values. Boxes contain the 50% of values falling between the 25th and 75th percentiles, whiskers lines that extend from the boxes represent the highest and lowest values for each subgroups. Statistical analysis was performed using non-parametric U Mann-Whitney test.

Mentions: As shown in Figure 4, MoDc from 4 CAPS patients produced significantly higher amount of IL-1β and IL-23 compared to 10 healthy controls and 4 SoJIA patients, whereas no relevant differences were observed in IL-6 secretion among the three subgroups.


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

Lasigliè D, Traggiai E, Federici S, Alessio M, Buoncompagni A, Accogli A, Chiesa S, Penco F, Martini A, Gattorno M - PLoS ONE (2011)

elevated level of IL-1β and IL-23 secreted by MoDCs of CAPS patients upon Zymosan stimulation.Secretion of IL-1β (A), IL-23 (B) and IL-6 (C) by MoDs upon 48 hours of challenge with or without Zymosan in 4 CAPS patients, 10 healthy controls and 4 active SoJIA patients. Bold horizontal lines represent median values. Boxes contain the 50% of values falling between the 25th and 75th percentiles, whiskers lines that extend from the boxes represent the highest and lowest values for each subgroups. Statistical analysis was performed using non-parametric U Mann-Whitney test.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3102666&req=5

pone-0020014-g004: elevated level of IL-1β and IL-23 secreted by MoDCs of CAPS patients upon Zymosan stimulation.Secretion of IL-1β (A), IL-23 (B) and IL-6 (C) by MoDs upon 48 hours of challenge with or without Zymosan in 4 CAPS patients, 10 healthy controls and 4 active SoJIA patients. Bold horizontal lines represent median values. Boxes contain the 50% of values falling between the 25th and 75th percentiles, whiskers lines that extend from the boxes represent the highest and lowest values for each subgroups. Statistical analysis was performed using non-parametric U Mann-Whitney test.
Mentions: As shown in Figure 4, MoDc from 4 CAPS patients produced significantly higher amount of IL-1β and IL-23 compared to 10 healthy controls and 4 SoJIA patients, whereas no relevant differences were observed in IL-6 secretion among the three subgroups.

Bottom Line: T helper 17 cells (T(H)-17) represent a lineage of effector T cells critical in host defence and autoimmunity.Secretion of IL-1β, IL-23 and IL-6 by monocyte derived dendritic cells (MoDCs), were quantified by ELISA assay.These findings further support the central role of IL-1β in the differentiation of T(H)17 in human inflammatory conditions.

View Article: PubMed Central - PubMed

Affiliation: Rheumatology Unit, Second Division of Pediatrics G. Gaslini Institute, Genoa, Italy.

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(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.

Show MeSH
Related in: MedlinePlus