Select hyperactivating NLRP3 ligands enhance the TH1- and TH17-inducing potential of human type 2 conventional dendritic cells.
Sci Signal
; 14(680)2021 04 27.
Article
em En
| MEDLINE
| ID: mdl-33906973
ABSTRACT
The detection of microorganisms and danger signals by pattern recognition receptors on dendritic cells (DCs) and the consequent formation of inflammasomes are pivotal for initiating protective immune responses. Although the activation of inflammasomes leading to secretion of the cytokine IL-1ß is typically accompanied by pyroptosis (an inflammatory form of lytic programmed cell death), some cells can survive and exist in a state of hyperactivation. Here, we found that the conventional type 2 DC (cDC2) subset is the major human DC subset that is transcriptionally and functionally poised for inflammasome formation and response without pyroptosis. When cDC2 were stimulated with ligands that relatively weakly activated the inflammasome, the cells did not enter pyroptosis but instead secreted IL-12 family cytokines and IL-1ß. These cytokines induced prominent T helper type 1 (TH1) and TH17 responses that were superior to those seen in response to Toll-like receptor (TLR) stimulation alone or to stronger, classical inflammasome ligands. These findings not only define the human cDC2 subpopulation as a prime target for the treatment of inflammasome-dependent inflammatory diseases but may also inform new approaches for adjuvant and vaccine development.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
/
Células Th1
/
Células Th17
/
Proteína 3 que Contém Domínio de Pirina da Família NLR
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article