First Author | Goettel JA | Year | 2016 |
Journal | Cell Rep | Volume | 17 |
Issue | 5 | Pages | 1318-1329 |
PubMed ID | 27783946 | Mgi Jnum | J:240807 |
Mgi Id | MGI:5896462 | Doi | 10.1016/j.celrep.2016.09.082 |
Citation | Goettel JA, et al. (2016) AHR Activation Is Protective against Colitis Driven by T Cells in Humanized Mice. Cell Rep 17(5):1318-1329 |
abstractText | Existing therapies for inflammatory bowel disease that are based on broad suppression of inflammation result in variable clinical benefit and unwanted side effects. A potential therapeutic approach for promoting immune tolerance is the in vivo induction of regulatory T cells (Tregs). Here we report that activation of the aryl hydrocarbon receptor using the non-toxic agonist 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) induces human Tregs in vitro that suppress effector T cells through a mechanism mediated by CD39 and Granzyme B. We then developed a humanized murine system whereby human CD4+ T cells drive colitis upon exposure to 2,4,6-trinitrobenzenesulfonic acid and assessed ITE as a potential therapeutic. ITE administration ameliorated colitis in humanized mice with increased CD39, Granzyme B, and IL10-secreting human Tregs. These results develop an experimental model to investigate human CD4+ T responses in vivo and identify the non-toxic AHR agonist ITE as a potential therapy for promoting immune tolerance in the intestine. |