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

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 in the current report. A transcriptome analysis of IECs in wildtype (WT) mice revealed that during colitis, I3C regulated select mucin proteins, which could be attributed to goblet cell development. To address this, experiments under in vivo colitis (mice) or in vitro colon organoid conditions were undertaken to determine how select mucin proteins were altered in the absence or presence of AhR in IECs during I3C treatment. Comparing WT to IEC-specific AhR knockout mice (AhRΔIEC), the results showed that AhR expression was essential in IECs for I3C-mediated protection during colitis. AhR-deficiency also impaired mucin protein expression, particularly mucin 2 (Muc2), independently of IL-22. Collectively, this report highlights the important role of AhR in direct regulation of Muc2. These results provide justification for future studies aimed at determining how AhR might regulate select mucins through mechanisms such as direct transcription binding to enhance production.

The Drosophila Mutagen-Sensitivity Gene mus109 Encodes DmDNA2.

The identification of mutants through forward genetic screens is the backbone of Drosophila genetics research, yet many mutants identified through these screens have yet to be mapped to the Drosophila genome. This is especially true of mutants that have been identified as mutagen-sensitive (mus), but have not yet been mapped to their associated molecular locus. Our study addressed the need for additional mus gene identification by determining the locus and exploring the function of the X-linked mutagen-sensitive gene mus109 using three available mutant alleles: mus109D1, mus109D2, and mus109lS. After first confirming that all three mus109 alleles were sensitive to methyl methanesulfonate (MMS) using complementation analysis, we used deletion mapping to narrow the candidate genes for mus109. Through DNA sequencing, we were able to determine that mus109 is the uncharacterized gene CG2990, which encodes the Drosophila ortholog of the highly conserved DNA2 protein that is important for DNA replication and repair. We further used the sequence and structure of DNA2 to predict the impact of the mus109 allele mutations on the final gene product. Together, these results provide a tool for researchers to further investigate the role of DNA2 in DNA repair processes in Drosophila.