AHR Activation Is Protective against Colitis Driven by T Cells in Humanized Mice

Cell Rep. 2016 Oct 25;17(5):1318-1329. doi: 10.1016/j.celrep.2016.09.082.


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.

Keywords: AHR; IBD; ITE; humanized mice; treg.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colitis / immunology*
  • Colitis / metabolism*
  • Disease Models, Animal
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Mice
  • Receptors, Aryl Hydrocarbon / metabolism*
  • T-Lymphocytes, Regulatory / immunology*
  • Thiazoles
  • Transforming Growth Factor beta1 / pharmacology
  • Trinitrobenzenesulfonic Acid


  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Receptors, Aryl Hydrocarbon
  • Thiazoles
  • Transforming Growth Factor beta1
  • Trinitrobenzenesulfonic Acid