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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Inflammation
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1444045

Regulation of Bacteroides acidifaciens by the aryl hydrocarbon receptor in IL-22-producing immune cells has sex-dependent consequential impact on colitis

Provisionally accepted
Chandani Mitchell Chandani Mitchell Shanieka Staley Shanieka Staley Michal C. Williams Michal C. Williams Archana Saxena Archana Saxena Raymond Bogdon Raymond Bogdon Kasie Roark Kasie Roark Michele Hailey Michele Hailey Kathryn Miranda Kathryn Miranda William Becker William Becker Nicholas Dopkins Nicholas Dopkins Maria M. Pena Maria M. Pena Kristen M. Hogan Kristen M. Hogan Maredith Baird Maredith Baird Kiesha Wilson Kiesha Wilson Prakash Nagarkatti Prakash Nagarkatti Mitzi Nagarkatti Mitzi Nagarkatti Philip B. Busbee Philip B. Busbee *
  • University of South Carolina, Columbia, United States

The final, formatted version of the article will be published soon.

    Colitis is an inflammatory bowel disease (IBD) characterized by immune cell dysregulation and alterations in the gut microbiome. In our previous report, we showed a natural product in cruciferous vegetables and ligand of the aryl hydrocarbon receptor (AhR), indole-3-carbinol (I3C), was able to reduce colitis-induced disease severity and microbial dysbiosis in an interleukin-22 (IL-22) dependent manner. In the current study, we performed single-cell RNA sequencing (scRNAseq) from colonocytes during colitis induction and supplementation with I3C and show how this treatment alters expression of genes involved in IL-22 signaling. To further define the role of IL-22 signaling in I3C-mediated protection during colitis and disease-associated microbial dysbiosis, we generated mice with AhR deficiency in RAR-related orphan receptor c (Rorc)-expressing cells (AhR ΔRorc ) which depletes this receptor in immune cells involved in production of IL-22. Colitis was induced in wildtype (WT), AhR ΔRorc , and littermate (LM) mice with or without I3C treatment. Results showed AhR ΔRorc mice lost the efficacy effects of I3C treatment which correlated with a loss of ability to increase IL-22 by innate lymphoid type 3 (ILC3s), not T helper 22 (Th22) cells. 16S rRNA microbiome profiling studies showed AhR ΔRorc mice were unable to regulate disease-associated increases in Bacteroides, which differed between males and females. Lastly, inoculation with a specific disease-associated Bacteroides species, Bacteroides acidifaciens (B. acidifaciens), was shown to exacerbate colitis in females, but not males. Collectively, this report highlights the cell and sex-specific role of AhR in regulating microbes that can impact colitis disease.

    Keywords: inflammatory bowel disease, Colitis, Aryl hydrocarbon receptor, Indole-3-carbinol, interleukin-22, innate lymphoid type 3 cells, Bacteroides acidifaciens, sex differences

    Received: 05 Jun 2024; Accepted: 31 Jul 2024.

    Copyright: © 2024 Mitchell, Staley, Williams, Saxena, Bogdon, Roark, Hailey, Miranda, Becker, Dopkins, Pena, Hogan, Baird, Wilson, Nagarkatti, Nagarkatti and Busbee. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Philip B. Busbee, University of South Carolina, Columbia, United States

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