| First Author | Dai B | Year | 2021 |
| Journal | Cell Rep Med | Volume | 2 |
| Issue | 8 | Pages | 100381 |
| PubMed ID | 34467254 | Mgi Jnum | J:350872 |
| Mgi Id | MGI:6880606 | Doi | 10.1016/j.xcrm.2021.100381 |
| Citation | Dai B, et al. (2021) Dual targeting of lymphocyte homing and retention through alpha4beta7 and alphaEbeta7 inhibition in inflammatory bowel disease. Cell Rep Med 2(8):100381 |
| abstractText | Anti-integrins are therapeutically effective for inflammatory bowel disease, yet the relative contribution of alpha4beta7 and alphaEbeta7 to gut lymphocyte trafficking is not fully elucidated. Here, we evaluate the effect of alpha4beta7 and alphaEbeta7 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 alpha4beta7 and alphaEbeta7 reduces CD8(+) T cell accumulation in the gut to a greater extent than blockade of either integrin alone. Anti-alphaEbeta7 reduces epithelial:T cell interactions and promotes egress of activated T cells from the mucosa into lymphatics. Inflammatory gene expression is greater in human intestinal alphaEbeta7(+) T cells. Etrolizumab-treated patients with CD display a treatment-specific reduction in inflammatory and cytotoxic intraepithelial lymphocytes (IEL) genes. Concurrent blockade of alpha4beta7 and alphaEbeta7 promotes reduction of cytotoxic IELs and inflammatory T cells in the gut mucosa through a stepwise inhibition of intestinal tissue entry and retention. |
