ICOS signaling limits regulatory T cell accumulation and function in visceral adipose tissue.
J Exp Med
; 218(6)2021 06 07.
Article
en En
| MEDLINE
| ID: mdl-33881452
ABSTRACT
A unique population of Foxp3+ regulatory T cells (TRs) resides in visceral adipose tissue (VAT) that regulates adipose inflammation and helps preserve insulin sensitivity. Inducible T cell co-stimulator (ICOS) is highly expressed on effector (e)TRs that migrate to nonlymphoid tissues, and contributes to their maintenance and function in models of autoimmunity. In this study, we report an unexpected cell-intrinsic role for ICOS expression and downstream phosphoinositide 3-kinase (PI3K) signaling in limiting the abundance, VAT-associated phenotype, and function of TRs specifically in VAT. Icos-/- mice and mice expressing a knock-in form of ICOS that cannot activate PI3K had increased VAT-TR abundance and elevated expression of canonical VAT-TR markers. Loss of ICOS signaling facilitated enhanced accumulation of TRs to VAT associated with elevated CCR3 expression, and resulted in reduced adipose inflammation and heightened insulin sensitivity in the context of a high-fat diet. Thus, we have uncovered a new and surprising molecular pathway that regulates VAT-TR accumulation and function.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Transducción de Señal
/
Tejido Adiposo
/
Linfocitos T Reguladores
/
Proteína Coestimuladora de Linfocitos T Inducibles
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
J Exp Med
Año:
2021
Tipo del documento:
Article