Increased interleukin-10 production by ASC-deficient CD4(+) T cells impairs bystander T-cell proliferation.

Détails

ID Serval
serval:BIB_F5CF21669AE3
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Increased interleukin-10 production by ASC-deficient CD4(+) T cells impairs bystander T-cell proliferation.
Périodique
Immunology
Auteur(s)
Narayan S., Kolly L., So A., Busso N.
ISSN
1365-2567 (Electronic)
ISSN-L
0019-2805
Statut éditorial
Publié
Date de publication
2011
Volume
134
Numéro
1
Pages
33-40
Langue
anglais
Résumé
Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is an important component of the inflammasome, functioning as an adaptor protein that facilitates the recruitment and activation of procaspases that in turn promote the maturation of interleukin-1β (IL-1β) and IL-18. Despite initial focus on the inflammatory properties of ASC there is emerging evidence that highlights the importance of ASC in facilitating adaptive immune responses. However, the cellular and molecular basis for the involvement of ASC in adaptive immunity remains largely unexplored. We have previously demonstrated that activated ASC-deficient T cells have dampened proliferative responses. We have therefore explored the underlying cellular mechanism(s) by which ASC regulates T-cell proliferation. We show that under activating conditions (anti-CD3/CD28 stimulation) in bulk T-cell cultures the presence of ASC(-/-)  CD4(+) T cells is sufficient to suppress the proliferative responses of neighbouring T cells. Furthermore, ASC(-/-)  CD4(+) T cells upon activation exhibit a suppressive cytokine profile, with elevated production of IL-10 and reduced secretion of T helper type 1 cytokines, interferon-γ and IL-2. This increase in IL-10 secretion within the activated ASC(-/-)  CD4(+) T-cell compartment was not associated with a proportional increase in conventional Foxp3(+) regulatory T (Treg) cells. Interestingly, when equal numbers of fluorescence-activated cell sorted ASC(+/+) and ASC(-/-) Treg cells (CD4(+)  CD44(intermediate/high)  CD25(+) ) were activated in vitro, the ASC(-/-) fraction produced significantly more IL-10 than their wild-type counterparts, suggesting that ASC(-/-) Treg cells have greater suppressive capacity. Collectively, these results imply that the ASC may influence the development and functioning of Treg cells.
Pubmed
Web of science
Open Access
Oui
Création de la notice
01/09/2011 9:55
Dernière modification de la notice
20/08/2019 17:22
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