TLR9 signalling activation via direct ligation and its functional consequences in CD4 + T cells.
Scand J Immunol
; 96(5)2022 Nov.
Article
em En
| MEDLINE
| ID: mdl-37406035
ABSTRACT
CpG Oligodeoxynucleotides (ODNs) are established TLR9 ligands; however, their functional responses in CD4+ T cells are believed to be independent of TLR9 and MyD88. We studied ligand-receptor interactions of ODN 2216 and TLR9 in human CD4+ T cells and assessed their consequences in terms of TLR9 signalling and cell phenotype. We demonstrated that the uptake of ODN 2216, a synthetic TLR9 agonist, is controlled by TLR9 signalling molecules and results in an increase in the expression of TLR9 signalling molecules, regulated via a feedback mechanism. Next, the uptake of ODN 2216 resulted in TLR9 signalling dependent but MyD88 independent increase in expression of TGF-ß. Finally, ODN 2216 treated CD4+ T cells showed an anti-inflammatory phenotype that was similar to Th3 type of regulatory T cells. These Th3-like cells were able to suppress the proliferation of untreated CD4+ T cells. Collectively, our results demonstrate a direct and interdependent relationship between ODN 2216 uptake and TLR9 signalling in CD4+ T cells. Our findings thus pave the way for future research to explore direct modulation of adaptive immune cells, using innate immune ligands, to subvert exaggerated inflammatory responses.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptor Toll-Like 9
/
Fator 88 de Diferenciação Mieloide
Limite:
Humans
Idioma:
En
Revista:
Scand J Immunol
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Índia