A Retinoid X Receptor Agonist Directed to the Large Intestine Ameliorates T-Cell-Mediated Colitis in Mice

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Induction of Intestinal Inflammation by Adoptive Transfer of CBir1 TCR Transgenic CD4+ T Cells to Immunodeficient Mice
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Induction of Intestinal Inflammation by Adoptive Transfer of CBir1 TCR Transgenic CD4+ T Cells to Immunodeficient Mice

Published on: December 16, 2021

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Ryohtaroh Matsumoto1, Daisuke Takahashi1, Masaki Watanabe2

  • 1Division of Biochemistry, Graduate School of Pharmaceutical Science and Faculty of Pharmacy, Keio University, Tokyo, Japan.

Frontiers in Pharmacology
|September 3, 2021
PubMed

Insights

A new Retinoid X receptor (RXR) agonist, NEt-3IB, targets the large intestine to treat inflammatory bowel diseases (IBDs). This targeted approach minimizes side effects associated with traditional RXR agonists.

Area of Science:

  • Molecular Endocrinology
  • Immunology
  • Gastroenterology

Background:

  • Retinoid X receptor (RXR) agonists show therapeutic potential for inflammatory diseases like inflammatory bowel diseases (IBDs).
  • Existing RXR agonists cause adverse effects due to upper intestinal absorption.
  • There is a need for RXR agonists with improved safety profiles and targeted delivery.

Purpose of the Study:

  • To develop and evaluate a novel, poorly absorbed RXR agonist, NEt-3IB, for targeted delivery to the large intestine.
  • To assess the efficacy of NEt-3IB in a murine model of T cell-mediated chronic colitis.

Main Methods:

  • Development of NEt-3IB, an RXR agonist with poor absorptive properties.
  • Pharmacokinetic studies to confirm large intestine delivery of NEt-3IB after oral administration.
  • Evaluation of NEt-3IB in a murine colitis model induced by CD45RBhighCD4+ T cell transfer.

Main Results:

  • NEt-3IB demonstrated successful delivery to the large intestine.
  • NEt-3IB treatment significantly suppressed chronic colitis development in mice.
  • Suppression of IFN-γ-producing Th1 cell expansion in the colon was observed.

Conclusions:

  • NEt-3IB is a promising large intestine-directed RXR agonist for treating IBDs.
  • Targeted delivery of NEt-3IB minimizes adverse effects associated with systemic absorption.
  • NEt-3IB offers a potential new therapeutic strategy for inflammatory bowel diseases.
Keywords:
NEt-3IBRXRTh1 cellscolitisinflammatory bowel disease

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