Aryl Hydrocarbon Receptor Regulates Muc2 Production Independently of IL-22 during Colitis

• DOI: 10.3390/ijms25042404
• Publication Date: 2024-02-19T10:39:56Z
• Authors: Archana Saxena; Chandani Mitchell; Raymond Bogdon; Kasie Roark; Kiesha Wilson; Shanieka Staley; Michelle Hailey; Michal Claire Wil...; Alex Rutkovsky; Prakash Nagarkatti; Mitzi Nagarkatti; Philip Brandon Bu...
• Keywords: Mucin 2; Knockout mouse

We previously reported that an aryl hydrocarbon receptor (AhR) ligand, indole-3-carbinol (I3C), was effective at reducing colitis severity through immune cell-mediated interleukin-22 (IL-22) production. Intestinal epithelial cells (IECs) are also involved in regulating colitis, so we investigated their AhR-mediated mechanisms the current report. A transcriptome analysis of IECs wildtype (WT) mice revealed during I3C regulated select mucin proteins, which could be attributed to goblet cell development. To address this, experiments under vivo (mice) or vitro colon organoid conditions were undertaken determine how proteins altered absence presence AhR treatment. Comparing WT IEC-specific knockout (AhRΔIEC), results showed expression essential for I3C-mediated protection colitis. AhR-deficiency impaired protein expression, particularly 2 (Muc2), independently IL-22. Collectively, this report highlights important role direct regulation Muc2. These provide justification future studies aimed determining might regulate mucins such as transcription binding enhance