Dual targeting of lymphocyte homing and retention through α4ß7 and αEß7 inhibition in inflammatory bowel disease.
Cell Rep Med
; 2(8): 100381, 2021 08 17.
Article
in En
| MEDLINE
| ID: mdl-34467254
ABSTRACT
Anti-integrins are therapeutically effective for inflammatory bowel disease, yet the relative contribution of α4ß7 and αEß7 to gut lymphocyte trafficking is not fully elucidated. Here, we evaluate the effect of α4ß7 and αEß7 blockade using a combination of murine models of gut trafficking and longitudinal gene expression analysis in etrolizumab-treated patients with Crohn's disease (CD). Dual blockade of α4ß7 and αEß7 reduces CD8+ T cell accumulation in the gut to a greater extent than blockade of either integrin alone. Anti-αEß7 reduces epithelialT cell interactions and promotes egress of activated T cells from the mucosa into lymphatics. Inflammatory gene expression is greater in human intestinal αEß7+ T cells. Etrolizumab-treated patients with CD display a treatment-specific reduction in inflammatory and cytotoxic intraepithelial lymphocytes (IEL) genes. Concurrent blockade of α4ß7 and αEß7 promotes reduction of cytotoxic IELs and inflammatory T cells in the gut mucosa through a stepwise inhibition of intestinal tissue entry and retention.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Lymphocytes
/
Inflammatory Bowel Diseases
/
Integrins
Limits:
Animals
Language:
En
Journal:
Cell Rep Med
Year:
2021
Document type:
Article
Affiliation country:
Estados Unidos