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Article

Involvement of Intestinal Epithelium Aryl Hydrocarbon Receptor Expression and 3, 3′-Diindolylmethane in Colonic Tertiary Lymphoid Tissue Formation

by
Erika L. Garcia-Villatoro
1,
Zachary S. Bomstein
2,
Kimberly F. Allred
1,2,
Evelyn S. Callaway
1,
Stephen Safe
3,
Robert S. Chapkin
1,4,
Arul Jayaraman
1,5 and
Clinton D. Allred
1,2,*
1
Department of Nutrition, Texas A&M University, College Station, TX 77843, USA
2
Department of Nutrition, University of North Carolina Greensboro, Greensboro, NC 27412, USA
3
Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77840, USA
4
Program in Integrative Nutrition & Complex Diseases, Texas A&M University, College Station, TX 77843, USA
5
Department of Chemical Engineering, Texas A&M University, College Station, TX 77843-3127, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2024, 25(18), 10153; https://doi.org/10.3390/ijms251810153
Submission received: 13 August 2024 / Revised: 18 September 2024 / Accepted: 19 September 2024 / Published: 21 September 2024
(This article belongs to the Special Issue Inflammatory Bowel Disease: Molecular Insights)

Abstract

Tertiary lymphoid tissues (TLTs) are adaptive immune structures that develop during chronic inflammation and may worsen or lessen disease outcomes in a context-specific manner. Immune cell activity governing TLT formation in the intestines is dependent on immune cell aryl hydrocarbon receptor (AhR) activation. Homeostatic immune cell activity in the intestines is further dependent on ligand activation of AhR in intestinal epithelial cells (IECs), yet whether AhR activation and signaling in IECs influences the formation of TLTs in the presence of dietary AhR ligands is not known. To this end, we used IEC-specific AhR deletion coupled with a mouse model of dextran sodium sulfate (DSS)-induced colitis to understand how dietary AhR ligand 3, 3′-diindolylmethane (DIM) influenced TLT formation. DIM consumption increased the size of TLTs and decreased T-cell aggregation to TLT sites in an IEC-specific manner. In DSS-exposed female mice, DIM consumption increased the expression of genes implicated in TLT formation (Interleukin-22, Il-22; CXC motif chemokine ligand 13, CXCL13) in an IEC AhR-specific manner. Conversely, in female mice without DSS exposure, DIM significantly reduced the expression of Il-22 or CXCL13 in iAhRKO mice, but this effect was not observed in WT animals. Our findings suggest that DIM affects the immunological landscape of TLT formation during DSS-induced colitis in a manner contingent on AhR expression in IECs and biological sex. Further investigations into specific immune cell activity, IEC-specific AhR signaling pathways, and dietary AhR ligand-mediated effects on TLT formation are warranted.
Keywords: colon; tertiary lymphoid tissues; aryl hydrocarbon receptor; DIM; intestinal epithelium colon; tertiary lymphoid tissues; aryl hydrocarbon receptor; DIM; intestinal epithelium

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MDPI and ACS Style

Garcia-Villatoro, E.L.; Bomstein, Z.S.; Allred, K.F.; Callaway, E.S.; Safe, S.; Chapkin, R.S.; Jayaraman, A.; Allred, C.D. Involvement of Intestinal Epithelium Aryl Hydrocarbon Receptor Expression and 3, 3′-Diindolylmethane in Colonic Tertiary Lymphoid Tissue Formation. Int. J. Mol. Sci. 2024, 25, 10153. https://doi.org/10.3390/ijms251810153

AMA Style

Garcia-Villatoro EL, Bomstein ZS, Allred KF, Callaway ES, Safe S, Chapkin RS, Jayaraman A, Allred CD. Involvement of Intestinal Epithelium Aryl Hydrocarbon Receptor Expression and 3, 3′-Diindolylmethane in Colonic Tertiary Lymphoid Tissue Formation. International Journal of Molecular Sciences. 2024; 25(18):10153. https://doi.org/10.3390/ijms251810153

Chicago/Turabian Style

Garcia-Villatoro, Erika L., Zachary S. Bomstein, Kimberly F. Allred, Evelyn S. Callaway, Stephen Safe, Robert S. Chapkin, Arul Jayaraman, and Clinton D. Allred. 2024. "Involvement of Intestinal Epithelium Aryl Hydrocarbon Receptor Expression and 3, 3′-Diindolylmethane in Colonic Tertiary Lymphoid Tissue Formation" International Journal of Molecular Sciences 25, no. 18: 10153. https://doi.org/10.3390/ijms251810153

APA Style

Garcia-Villatoro, E. L., Bomstein, Z. S., Allred, K. F., Callaway, E. S., Safe, S., Chapkin, R. S., Jayaraman, A., & Allred, C. D. (2024). Involvement of Intestinal Epithelium Aryl Hydrocarbon Receptor Expression and 3, 3′-Diindolylmethane in Colonic Tertiary Lymphoid Tissue Formation. International Journal of Molecular Sciences, 25(18), 10153. https://doi.org/10.3390/ijms251810153

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