| First Author | Sun H | Year | 2020 |
| Journal | Cell Mol Gastroenterol Hepatol | Volume | 9 |
| Issue | 3 | Pages | 369-385 |
| PubMed ID | 31707128 | Mgi Jnum | J:336583 |
| Mgi Id | MGI:6718097 | Doi | 10.1016/j.jcmgh.2019.10.012 |
| Citation | Sun H, et al. (2020) beta7 Integrin Inhibition Can Increase Intestinal Inflammation by Impairing Homing of CD25(hi)FoxP3(+) Regulatory T Cells. Cell Mol Gastroenterol Hepatol 9(3):369-385 |
| abstractText | BACKGROUND & AIMS: Integrin alpha4beta7 mediates lymphocyte trafficking to the gut and gut-associated lymphoid tissues, a process critical for recruitment of effector lymphocytes from the circulation to the gut mucosa in inflammatory bowel disease (IBD) and murine models of intestinal inflammation. Antibody blockade of beta7 integrins generally is efficacious in IBD; however, some patients fail to respond, and a few patients can experience exacerbations. This study examined the effects of loss of beta7 integrin function in murine models of IBD. METHODS: In a mouse IBD model caused by lack of interleukin 10, a cytokine important in CD25(hi)FoxP3(+) regulatory T cell (Treg) function, genetic deletion of beta7 integrin or antibody blockade of alpha4beta7-mucosal addressin cell adhesion molecule-1 interaction paradoxically exacerbated colitis. RESULTS: Loss of beta7 impaired the capacity of Tregs homing to the gut and therefore suppress intestinal inflammation in an adoptive T-cell transfer model; however, the intrinsic suppressive function of beta7-deficient Tregs remained intact, indicating that the beta7 deficiency selectively impacts gut homing. Deletion of beta7 integrin did not worsen colitis in an acute dextran sodium sulfate model in which Treg number and function were normal. CONCLUSIONS: In Integrin subunit beta (Itgb)7(-/-)Il10(-/-) mice, loss of beta7-dependent Treg homing to gut-associated lymphoid tissues combined with loss of intrinsic Treg function exacerbated intestinal inflammation. These results suggest that IBD patients with reduced CD25(hi)FoxP3(+) Treg numbers or function or lack of interleukin 10 could be at risk for failure of alpha4beta7 blocking therapy. |
