Epithelial IL-15 Is a Critical Regulator of γδ Intraepithelial Lymphocyte Motility within the Intestinal Mucosa.
J Immunol
; 201(2): 747-756, 2018 07 15.
Article
em En
| MEDLINE
| ID: mdl-29884699
ABSTRACT
Intraepithelial lymphocytes (IELs) expressing the γδ TCR (γδ IELs) provide continuous surveillance of the intestinal epithelium. However, the mechanisms regulating the basal motility of these cells within the epithelial compartment have not been well defined. We investigated whether IL-15 contributes to γδ IEL localization and migratory behavior in addition to its role in IEL differentiation and survival. Using advanced live cell imaging techniques in mice, we find that compartmentalized overexpression of IL-15 in the lamina propria shifts the distribution of γδ T cells from the epithelial compartment to the lamina propria. This mislocalization could be rescued by epithelial IL-15 overexpression, indicating that epithelial IL-15 is essential for γδ IEL migration into the epithelium. Furthermore, in vitro analyses demonstrated that exogenous IL-15 stimulates γδ IEL migration into cultured epithelial monolayers, and inhibition of IL-2Rß significantly attenuates the basal motility of these cells. Intravital microscopy showed that impaired IL-2Rß signaling induced γδ IEL idling within the lateral intercellular space, which resulted in increased early pathogen invasion. Similarly, the redistribution of γδ T cells to the lamina propria due to local IL-15 overproduction also enhanced bacterial translocation. These findings thus reveal a novel role for IL-15 in mediating γδ T cell localization within the intestinal mucosa and regulating γδ IEL motility and patrolling behavior as a critical component of host defense.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
/
Interleucina-15
/
Linfócitos Intraepiteliais
/
Mucosa Intestinal
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2018
Tipo de documento:
Article