Chemokine receptor CCR9 suppresses the differentiation of CD4+CD8αα+ intraepithelial T cells in the gut.
Mucosal Immunol
; 15(5): 882-895, 2022 05.
Article
en En
| MEDLINE
| ID: mdl-35778600
ABSTRACT
The chemokine receptor CCR9 equips T cells with the ability to respond to CCL25, a chemokine that is highly expressed in the thymus and the small intestine (SI). Notably, CCR9 is mostly expressed on CD8 but not on CD4 lineage T cells, thus imposing distinct tissue tropism on CD4 and CD8 T cells. The molecular basis and the consequences for such a dichotomy, however, have not been fully examined and explained. Here, we demonstrate that the forced expression of CCR9 interferes with the tissue trafficking and differentiation of CD4 T cells in SI intraepithelial tissues. While CCR9 overexpression did not alter CD4 T cell generation in the thymus, the forced expression of CCR9 was detrimental for the proper tissue distribution of CD4 T cells in the periphery, and strikingly also for their terminal differentiation in the gut epithelium. Specifically, the differentiation of SI epithelial CD4 T cells into immunoregulatory CD4+CD8αα+ T cells was impaired by overexpression of CCR9 and conversely increased by the genetic deletion of CCR9. Collectively, our results reveal a previously unappreciated role for CCR9 in the tissue homeostasis and effector function of CD4 T cells in the gut.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Receptores CCR
/
Linfocitos Intraepiteliales
Idioma:
En
Revista:
Mucosal Immunol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos