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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

Analysis of IL-17 and IL-6 serum concentrations and peripheral CD4+ T cell phenotype.IL-17 (panel A) and IL-6 (panel B) serum levels were measured in 10 active CAPS patients, 20 active SoJIA patients and 20 healthy controls by ELISA. C–D) Ex-vivo analysis of circulating CCR6+ (panel B) and CD161+ (panel C) memory T cells (CD4+CD45RA−) in the same three subgroups. Heterogeneity test among groups was evaluated using the non parametric Kruskal-Wallis test (upper right of each graph). Post-hoc analysis with non-parametric U Mann-Whitney test revealed the difference among the three subgroups.
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pone-0020014-g001: Analysis of IL-17 and IL-6 serum concentrations and peripheral CD4+ T cell phenotype.IL-17 (panel A) and IL-6 (panel B) serum levels were measured in 10 active CAPS patients, 20 active SoJIA patients and 20 healthy controls by ELISA. C–D) Ex-vivo analysis of circulating CCR6+ (panel B) and CD161+ (panel C) memory T cells (CD4+CD45RA−) in the same three subgroups. Heterogeneity test among groups was evaluated using the non parametric Kruskal-Wallis test (upper right of each graph). Post-hoc analysis with non-parametric U Mann-Whitney test revealed the difference among the three subgroups.

Mentions: Serum IL-17 was measured in 10 active NLPR3-mutated CAPS patients compared to 20 healthy controls and 20 SoJIA patients. As shown in Figure 1A, IL-17 was significantly higher in CAPS patients (median 5,1 pg/ml range:0–14.4) when compared to healthy controls [0.4 pg/ml, 0–6.5 pg/ml) (p = 0.04). A slight elevation of serum IL-17 was also observed in some active SoJIA patients (1.9 pg/ml, 0–8.6 pg/ml), with no statistical differences with either CAPS patients or healthy controls (Figure 1A).


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)

Analysis of IL-17 and IL-6 serum concentrations and peripheral CD4+ T cell phenotype.IL-17 (panel A) and IL-6 (panel B) serum levels were measured in 10 active CAPS patients, 20 active SoJIA patients and 20 healthy controls by ELISA. C–D) Ex-vivo analysis of circulating CCR6+ (panel B) and CD161+ (panel C) memory T cells (CD4+CD45RA−) in the same three subgroups. Heterogeneity test among groups was evaluated using the non parametric Kruskal-Wallis test (upper right of each graph). Post-hoc analysis with non-parametric U Mann-Whitney test revealed the difference among the three subgroups.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0020014-g001: Analysis of IL-17 and IL-6 serum concentrations and peripheral CD4+ T cell phenotype.IL-17 (panel A) and IL-6 (panel B) serum levels were measured in 10 active CAPS patients, 20 active SoJIA patients and 20 healthy controls by ELISA. C–D) Ex-vivo analysis of circulating CCR6+ (panel B) and CD161+ (panel C) memory T cells (CD4+CD45RA−) in the same three subgroups. Heterogeneity test among groups was evaluated using the non parametric Kruskal-Wallis test (upper right of each graph). Post-hoc analysis with non-parametric U Mann-Whitney test revealed the difference among the three subgroups.
Mentions: Serum IL-17 was measured in 10 active NLPR3-mutated CAPS patients compared to 20 healthy controls and 20 SoJIA patients. As shown in Figure 1A, IL-17 was significantly higher in CAPS patients (median 5,1 pg/ml range:0–14.4) when compared to healthy controls [0.4 pg/ml, 0–6.5 pg/ml) (p = 0.04). A slight elevation of serum IL-17 was also observed in some active SoJIA patients (1.9 pg/ml, 0–8.6 pg/ml), with no statistical differences with either CAPS patients or healthy controls (Figure 1A).

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