Year: 2016
Type: article
Abstract: 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.
Source: Cell Reports
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,620
Funders: Crohn's and Colitis Foundation of America, Beth Israel Deaconess Medical Center, Boston Children's Hospital, Leona M. and Harry B. Helmsley Charitable Trust, Crohn's and Colitis Foundation, National Institutes of Health, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Environmental Health Sciences
Awards: G1444796925, Central Nervous System Autoimmunity and Immunoregulation in the Zebrafish, Central Nervous System Autoimmunity and Immunoregulation in the Zebrafish, Role of aryl hydrocarbon receptor in IL-10 producing Tr1 regulatory cells, G2887981597, G3435626911, G4672309340, G5162837516, G6901752016, Role of aryl hydrocarbon receptor in IL-10 producing Tr1 regulatory cells, Investigating cross-regulation of the microbiome and mucosal immune system using humanized mice, Regulation of CNS Autoimmunity, G9000271605, G9000346841, Training in Pediatric Gastroenterology, Hepatology, and Nutrition, Role of AHR in Dendritic Cells in the Control of CNS Autoimmunity, Integrated Epithelial and Muscosal Biology
OpenAlex ID: W2537641617