Th17 Archives - World Asthma Foundation

Vitamin D reduces the differentiation and expansion of Th17 cells in young asthmatic children.

Immunobiology. 2014 Jul 22;

Authors: Hamzaoui A, Berraïes A, Hamdi B, Kaabachi W, Ammar J, Hamzaoui K

Abstract
Vitamin D [25(OH)D3] deficiency has been associated with asthma as in many inflammatory and autoimmune pathologies; however, there is still a lack of data about the effects of administration of vitamin D in immune regulation in young asthmatic patients. In this study, we investigated its inhibitory effect on the immune response in young asthmatic patients and the possible mechanisms involved. Peripheral blood CD4(+) T cells from 10 asthmatic patients and 10 healthy controls were cultured under Th17 polarizing conditions in the presence or absence of [25(OH)D3], IL-17 cytokine production was determined by ELISA and flow cytometry. Messenger RNA (mRNA) expression of several factors related to Th17 cell function was determined by real-time PCR. The effect of [25(OH)D3]-treated dendritic cells (DCs) on CD4(+) T cell response was determined by ELISA and flow cytometry. Stimulation of naive CD4(+) T cells under Th17 polarizing conditions showed a higher Th17 cell differentiation in asthmatic patients than healthy controls. The addition of [25(OH)D3] significantly inhibited Th17 cell differentiation both in patients [P<0.001] and in normal controls [P=0.001] in a dose-dependent way. [25(OH)D3] was able to inhibit the gene expression of RORC, IL-17, IL-23R, and CCR6. [25(OH)D3]-treated DCs significantly inhibited IL-17 production [P=0.002] and decreased the percentage of CD4(+)IL-17(+) [P=0.007] in young asthmatics. The findings suggest that the inhibitory effect of [25(OH)D3] on the Th17 response was mediated via both T cells and DCs. DCs pathway is involved in the direct inhibition of 25(OH)D3 on Th17 cell differentiation in young asthmatics.

PMID: 25128460 [PubMed – as supplied by publisher]

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Inflammasome – IL-1 – Th17 response in allergic lung inflammation.

J Mol Cell Biol. 2011 Dec 6;

Authors: Besnard AG, Togbe D, Couillin I, Tan Z, Zheng SG, Erard F, Le Bert M, Quesniaux V, Ryffel B

Abstract
Allergic asthma has increased dramatically in prevalence and severity over the last three decades. Both clinical and experimental data support an important role of Th2 cell response in the allergic response. Recent investigations revealed that airway exposure to allergen in sensitized individuals causes the release of ATP and uric acid activating the NLRP3 inflammasome complex and caspase-1 cleaving pro-IL-1? to mature IL-1?. The production of pro-IL-1? requires a TLR4 signal which is provided by the allergen. IL-1? creates a pro-inflammatory milieu with the production of IL-6 and chemokines which mobilize neutrophils and enhance Th17 cell differentiation in the lung. Here, we review our results showing that NLRP3 inflammasome activation is required to develop allergic airway inflammation in mice and that IL-17 and IL-22 production by Th17 plays a critical role in established asthma. Therefore, inflammasome activation leading to IL-1? production contributes to the control of allergic asthma by enhancing Th17 cell differentiation.

PMID: 22147847 [PubMed – as supplied by publisher]

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