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Representations of the Aryl Hydrocarbon Receptor.  From Szöllősi et al. 2016 and Tagliabue et al. 2019 and Gruszcyk et al. 2022.

AhR 3D.jpg

The Aryl Hydrocarbon Receptor

Healthy microbiota on the skin and in the colon produce naturally-occurring aryl hydrocarbon receptor (AhR) agonists that play an important role in keeping our immune system in balance. AhR activation has been associated with decreased T-helper 17 activity and increased T-regulatory cell differentiation, regulation of inflammatory cytokines, and increased barrier function. Several inflammatory diseases such as inflammatory bowel disease, psoriasis, and hidradenitis suppurativa have been associated with defects in AhR signaling. Azora’s small molecule formulations are designed to locally activate the AhR in the skin and in the colon to rebalance the body’s natural immune response mechanisms in order to treat serious inflammatory diseases. 

Key Publications

  • Saiki JP, Andreasson JO, Grimes KV, Frumkin LR, Sanjines E, Davidson MG, Park KT, Limketkai B. Treatment-refractory ulcerative colitis responsive to indigo naturalis. BMJ Open Gastroenterol. 2021 Dec;8(1):e000813. doi: 10.1136/bmjgast-2021-000813. PMID: 34969665.

  • Stockinger B, Shah K, Wincent E. AHR in the intestinal microenvironment: safeguarding barrier function. Nat Rev Gastroenterol Hepatol. 2021 Aug;18(8):559-570. doi: 10.1038/s41575-021-00430-8. Epub 2021 Mar 19. PMID: 33742166; PMCID: PMC7611426.

  • Gruszczyk J, Grandvuillemin L, Lai-Kee-Him J, Paloni M, Savva CG, Germain P, Grimaldi M, Boulahtouf A, Kwong HS, Bous J, Ancelin A, Bechara C, Barducci A, Balaguer P, Bourguet W. Cryo-EM structure of the agonist-bound Hsp90-XAP2-AHR cytosolic complex. Nat Commun. 2022 Nov 16;13(1):7010. doi: 10.1038/s41467-022-34773-w. PMID: 36385050; PMCID: PMC9668932.

  • Uberoi A, Bartow-McKenney C, Zheng Q, Flowers L, Campbell A, Knight SAB, Chan N, Wei M, Lovins V, Bugayev J, Horwinski J, Bradley C, Meyer J, Crumrine D, Sutter CH, Elias P, Mauldin E, Sutter TR, Grice EA. Commensal microbiota regulates skin barrier function and repair via signaling through the aryl hydrocarbon receptor. Cell Host Microbe. 2021 Aug 11;29(8):1235-1248.e8. doi: 10.1016/j.chom.2021.05.011. Epub 2021 Jul 1. PMID: 34214492; PMCID: PMC8364505.

  • Guenin-Macé L, Morel JD, Doisne JM, Schiavo A, Boulet L, Mayau V, Goncalves P, Duchatelet S, Hovnanian A, Bondet V, Duffy D, Ungeheuer MN, Delage M, Nassif A, Di Santo JP, Demangel C. Dysregulation of tryptophan catabolism at the host-skin microbiota interface in hidradenitis suppurativa. JCI Insight. 2020 Oct 15;5(20):e140598. doi: 10.1172/jci.insight.140598. PMID: 32970636; PMCID: PMC7605522.

  • Lamas B, Richard ML, Leducq V, Pham HP, Michel ML, Da Costa G, Bridonneau C, Jegou S, Hoffmann TW, Natividad JM, Brot L, Taleb S, Couturier-Maillard A, Nion-Larmurier I, Merabtene F, Seksik P, Bourrier A, Cosnes J, Ryffel B, Beaugerie L, Launay JM, Langella P, Xavier RJ, Sokol H. CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands. Nat Med. 2016 Jun;22(6):598-605. doi: 10.1038/nm.4102. Epub 2016 May 9. PMID: 27158904; PMCID: PMC5087285.

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