{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T10:28:16Z","timestamp":1784543296595,"version":"3.55.0"},"reference-count":120,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:00:00Z","timestamp":1760054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, plays a crucial role in regulating immune homeostasis, inflammatory responses, and intestinal barrier function. Indole compounds and their derivatives are ligands of AHR, which can activate the AHR signal transduction pathway and show significant regulatory potential in various inflammatory and immune diseases. Cystic fibrosis (CF) is a life-threatening autosomal recessive genetic disorder. Cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction affects multiple systems throughout the body. The core of its pathological process is chronic infection, abnormal inflammation, and tissue damage caused by mucus accumulation. Exploring alternative or adjunctive therapeutic strategies targeting pathological pathways downstream of CFTR is of significant importance. The aim of the present study is to explore the multiple beneficial effects that indole compounds may exert in regulating pulmonary infection and inflammation, repairing intestinal barrier function, and regulating immune homeostasis in CF patients by activating the AHR signaling pathway. Additionally, this study discusses the risks and challenges associated with developing indole compounds as CF drugs, offering a novel research approach distinct from traditional CFTR modulators for creating new CF therapeutics.<\/jats:p>","DOI":"10.3390\/ijms26209876","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:34:08Z","timestamp":1760114048000},"page":"9876","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Targeting the Aryl Hydrocarbon Receptor: The Potential of Indole Compounds in the Treatment of Cystic Fibrosis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-5188-9225","authenticated-orcid":false,"given":"Sen","family":"Hou","sequence":"first","affiliation":[{"name":"School of Basic Medicine, Jiamusi University, Jiamusi 154007, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingkun","family":"Yue","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Jiamusi University, Jiamusi 154007, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Hou","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Jiamusi University, Jiamusi 154007, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingtian","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Jiamusi University, Jiamusi 154007, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Elias, A.E., McBain, A.J., Aldehalan, F.A., Taylor, G., and O\u2019Neill, C.A. (2024). Activation of the aryl hydrocarbon receptor via indole derivatives is a common feature in skin bacterial isolates. J. Appl. Microbiol., 135.","DOI":"10.1093\/jambio\/lxae273"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Abu-Hashem, A.A., and Al-Hussain, S.A. (2022). Design, Synthesis of New 1,2,4-Triazole\/1,3,4-Thiadiazole with Spiroindoline, Imidazo[4,5-b]quinoxaline and Thieno[2,3-d]pyrimidine from Isatin Derivatives as Anticancer Agents. Molecules, 27.","DOI":"10.3390\/molecules27030835"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1038\/s41586-023-05854-7","article-title":"CFTR function, pathology and pharmacology at single-molecule resolution","volume":"616","author":"Levring","year":"2023","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Kleinfelder, K., Somenza, E., Farinazzo, A., Conti, J., Lotti, V., Latorre, R.V., Rodella, L., Massella, A., Tomba, F., and Bertini, M. (2023). CFTR Modulators Rescue the Activity of CFTR in Colonoids Expressing the Complex Allele p.[R74W;V201M;D1270N]\/dele22_24. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24065199"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.pan.2024.03.005","article-title":"CFTR function is impaired in a subset of patients with pancreatitis carrying rare CFTR variants","volume":"24","author":"Angyal","year":"2024","journal-title":"Pancreatology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1113\/JP285702","article-title":"Role of CFTR in diabetes-induced pancreatic ductal fluid and HCO3\u2212 secretion","volume":"602","author":"Hegyi","year":"2024","journal-title":"J. Physiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1164\/rccm.202309-1565OC","article-title":"Pulmonary Ionocytes Regulate Airway Surface Liquid pH in Primary Human Bronchial Epithelial Cells","volume":"210","author":"Luan","year":"2024","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/j.devcel.2020.07.002","article-title":"Acidic Submucosal Gland pH and Elevated Protein Concentration Produce Abnormal Cystic Fibrosis Mucus","volume":"54","author":"Xie","year":"2020","journal-title":"Dev. Cell."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Hanssens, L.S., Duchateau, J., and Casimir, G.J. (2021). CFTR Protein: Not Just a Chloride Channel?. Cells, 10.","DOI":"10.3390\/cells10112844"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5732","DOI":"10.3748\/wjg.v25.i38.5732","article-title":"Role of ion channels in gastrointestinal cancer","volume":"25","author":"Anderson","year":"2019","journal-title":"World J. Gastroenterol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"27942","DOI":"10.1074\/jbc.M606449200","article-title":"Airway surface liquid volume regulates ENaC by altering the serine protease-protease inhibitor balance: A mechanism for sodium hyperabsorption in cystic fibrosis","volume":"281","author":"Myerburg","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/s41586-018-0393-7","article-title":"A revised airway epithelial hierarchy includes CFTR-expressing ionocytes","volume":"560","author":"Montoro","year":"2018","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s13023-024-03522-1","article-title":"Progression and mortality of patients with cystic fibrosis in China","volume":"20","author":"Zhou","year":"2025","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Gr\u00fcnewaldt, A., and Rohde, G. (2025). Retrospective cohort study of adult patients with cystic fibrosis supported with venovenous extracorporeal membrane oxygenation (VV ECMO) at a large German cystic fibrosis center. BMC Pulm. Med., 25.","DOI":"10.1186\/s12890-025-03745-3"},{"key":"ref_15","first-page":"101094","article-title":"The intermittent intrapulmonary deflation technique for airway clearance in patients with cystic fibrosis: A randomized trial","volume":"86","author":"Aubriot","year":"2024","journal-title":"Respir. Med. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1016\/j.jpedsurg.2021.02.047","article-title":"BAPS-CASS Early management of meconium ileus in infants with cystic fibrosis: A prospective population cohort study","volume":"56","author":"Long","year":"2021","journal-title":"J. Pediatr. Surg."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6668","DOI":"10.1038\/s41467-024-50641-1","article-title":"Allosteric inhibition of CFTR gating by CFTRinh-172 binding in the pore","volume":"15","author":"Gao","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e202012625","DOI":"10.1085\/jgp.202012625","article-title":"The molecular evolution of function in the CFTR chloride channel","volume":"153","author":"Infield","year":"2021","journal-title":"J. Gen. Physiol."},{"key":"ref_19","first-page":"100388","article-title":"Testicular function and fertility outcomes in males with CF: A multi center retrospective study of men with congenital bilateral absence of the vas deferens based on CFTR mutation status","volume":"40","author":"Cannarella","year":"2025","journal-title":"J. Clin. Transl. Endocrinol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Jathal, I., Stransky, O.M., Wright, C.E., Prangley, A., Tangpricha, V., Jain, R., Taylor-Cousar, J.L., Hughan, K.S., Ladores-Barrett, S., and West, N.E. (2025). Fertility and family-building experiences and perspectives of males with cystic fibrosis. Reprod. Biol. Endocrinol., 23.","DOI":"10.1186\/s12958-025-01417-9"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Borgo, C., D\u2019Amore, C., Capurro, V., Tomati, V., Pedemonte, N., Bosello Travain, V., and Salvi, M. (2024). SUMOylation Inhibition Enhances Protein Transcription under CMV Promoter: A Lesson from a Study with the F508del-CFTR Mutant. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25042302"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1016\/j.jcf.2020.04.010","article-title":"Accumulation and persistence of ivacaftor in airway epithelia with prolonged treatment","volume":"19","author":"Cholon","year":"2020","journal-title":"J. Cyst. Fibros."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/978-1-4939-3804-9_7","article-title":"Investigating Alternative Transport of Integral Plasma Membrane Proteins from the ER to the Golgi: Lessons from the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)","volume":"1459","author":"Amaral","year":"2016","journal-title":"Methods Mol. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.1016\/S0140-6736(16)00576-6","article-title":"Cystic fibrosis","volume":"388","author":"Elborn","year":"2016","journal-title":"Lancet"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"McDonald, E.F., Woods, H., Smith, S.T., Kim, M., Schoeder, C.T., Plate, L., and Meiler, J. (2022). Structural Comparative Modeling of Multi-Domain F508del CFTR. Biomolecules, 12.","DOI":"10.3390\/biom12030471"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Thavamani, A., Salem, I., Sferra, T.J., and Sankararaman, S. (2021). Impact of Altered Gut Microbiota and Its Metabolites in Cystic Fibrosis. Metabolites, 11.","DOI":"10.3390\/metabo11020123"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"20503121231225874","DOI":"10.1177\/20503121231225874","article-title":"Elexacaftor-tezacaftor-ivacaftor for cystic fibrosis with Phe508del mutation: Evidence from randomized controlled trials","volume":"12","author":"He","year":"2024","journal-title":"SAGE Open Med."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Meng, X., and Ford, R.C. (2024). Investigation of F508del CFTR unfolding and a search for stabilizing small molecules. Arch. Biochem. Biophys., 758.","DOI":"10.1016\/j.abb.2024.110050"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1007\/s41030-024-00269-9","article-title":"A Retrospective, Longitudinal Registry Study on the Long-Term Durability of Ivacaftor Treatment in People with Cystic Fibrosis","volume":"10","author":"Merlo","year":"2024","journal-title":"Pulm. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.jcf.2021.07.018","article-title":"Lumacaftor-ivacaftor effects on cystic fibrosis-related liver involvement in adolescents with homozygous F508 del-CFTR","volume":"21","author":"Drummond","year":"2022","journal-title":"J. Cyst. Fibros."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Bacalhau, M., Camargo, M., Magalh\u00e3es-Ghiotto, G.A.V., Drumond, S., Castelletti, C.H.M., and Lopes-Pacheco, M. (2023). Elexacaftor-Tezacaftor-Ivacaftor: A Life-Changing Triple Combination of CFTR Modulator Drugs for Cystic Fibrosis. Pharmaceuticals, 16.","DOI":"10.3390\/ph16030410"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6234","DOI":"10.1038\/s41467-022-33858-w","article-title":"Structural insight into the ligand binding mechanism of aryl hydrocarbon receptor","volume":"13","author":"Dai","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.str.2022.12.013","article-title":"Cryo-EM structure of the cytosolic AhR complex","volume":"31","author":"Wen","year":"2023","journal-title":"Structure"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1038\/s41573-025-01172-x","article-title":"The aryl hydrocarbon receptor: A rehabilitated target for therapeutic immune modulation","volume":"24","author":"Polonio","year":"2025","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Sondermann, N.C., Fa\u00dfbender, S., Hartung, F., H\u00e4t\u00e4l\u00e4, A.M., Rolfes, K.M., Vogel, C.F.A., and Haarmann-Stemmann, T. (2023). Functions of the aryl hydrocarbon receptor (AHR) beyond the canonical AHR\/ARNT signaling pathway. Biochem. Pharmacol., 208.","DOI":"10.1016\/j.bcp.2022.115371"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1093\/rheumatology\/ken259","article-title":"A role for the aryl hydrocarbon receptor and the dioxin TCDD in rheumatoid arthritis","volume":"47","author":"Kobayashi","year":"2008","journal-title":"Rheumatology"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"You, Y., Cai, B., Zhu, C., Zhou, Z., Xu, J., Huang, L., Jie, L., and Du, H. (2025). 3,3\u2032-diindolylmethane, from cruciferous vegetables, ameliorates cigarette smoke-induced inflammatory amplification in CIA model mice by targeting the AhR\/NF-\u03baB crosstalk. J. Nutr. Biochem., 143.","DOI":"10.1016\/j.jnutbio.2025.109953"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Sawa-Wejksza, K., Parada-Turska, J., and Turski, W. (2025). The Pharmacological Evidences for the Involvement of AhR and GPR35 Receptors in Kynurenic Acid-Mediated Cytokine and Chemokine Secretion by THP-1-Derived Macrophages. Molecules, 30.","DOI":"10.3390\/molecules30153133"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Ishihara, Y., Kado, S.Y., Bein, K.J., He, Y., Pouraryan, A.A., Urban, A., Haarmann-Stemmann, T., Sweeney, C., and Vogel, C.F.A. (2022). Aryl Hydrocarbon Receptor Signaling Synergizes with TLR\/NF-\u03baB-Signaling for Induction of IL-22 Through Canonical and Non-Canonical AhR Pathways. Front. Toxicol., 3.","DOI":"10.3389\/ftox.2021.787360"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Wang, Y.N., Wu, X., Shan, Q.Y., Yang, Q., Yu, X.Y., Yang, J.H., Miao, H., Cao, G., and Zhao, Y.Y. (2025). Acteoside-containing caffeic acid is bioactive functional group of antifibrotic effect by suppressing inflammation via inhibiting AHR nuclear translocation in chronic kidney disease. Acta Pharmacol. Sin., 1\u201314.","DOI":"10.1038\/s41401-025-01598-4"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"112288","DOI":"10.1016\/j.yexcr.2020.112288","article-title":"Aryl hydrocarbon receptor mediates Jak2\/STAT3 signaling for non-small cell lung cancer stem cell maintenance","volume":"396","author":"Xiong","year":"2020","journal-title":"Exp. Cell Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"117874","DOI":"10.1016\/j.jep.2024.117874","article-title":"Shaoyao decoction improves damp-heat colitis by activating the AHR\/IL-22\/STAT3 pathway through tryptophan metabolism driven by gut microbiota","volume":"326","author":"Zhang","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s10565-019-09499-z","article-title":"Down-regulation of aryl hydrocarbon receptor intensifies carcinogen-induced retinal lesion via SOCS3-STAT3 signaling","volume":"36","author":"Tsai","year":"2020","journal-title":"Cell Biol. Toxicol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Wang, L., Cheng, H., Wang, X., Zhu, F., Tian, N., Xu, Z., Yin, H., Liang, M., Yang, X., and Liu, X. (2024). Deubiquitination of aryl hydrocarbon receptor by USP21 negatively regulates T helper 17 cell differentiation. J. Leukoc. Biol., 117.","DOI":"10.1093\/jleuko\/qiae148"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/j.tips.2025.05.003","article-title":"Emerging approaches for antagonizing the aryl hydrocarbon receptor","volume":"46","author":"Mani","year":"2025","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Veland, N., Gleneadie, H.J., Brown, K.E., Sardini, A., Pombo, J., Dimond, A., Burns, V., Sarkisyan, K., Schiering, C., and Webster, Z. (2024). Bioluminescence imaging of Cyp1a1-luciferase reporter mice demonstrates prolonged activation of the aryl hydrocarbon receptor in the lung. Commun. Biol., 7.","DOI":"10.1038\/s42003-024-06089-6"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Zhou, L., Song, W., Liu, T., Yan, T., He, Z., He, W., Lv, J., Zhang, S., Dai, X., and Yuan, L. (2024). Multi-omics insights into anti-colitis benefits of the synbiotic and postbiotic derived from wheat bran arabinoxylan and Limosilactobacillus reuteri. Int. J. Biol. Macromol., 278.","DOI":"10.1016\/j.ijbiomac.2024.134860"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1186\/s13098-025-01837-y","article-title":"Unraveling the complexities of diet induced obesity and glucolipid dysfunction in metabolic syndrome","volume":"17","author":"Dutta","year":"2025","journal-title":"Diabetol. Metab. Syndr."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"113231","DOI":"10.1016\/j.ejmech.2021.113231","article-title":"Indole scaffolds as a promising class of the aryl hydrocarbon receptor ligands","volume":"215","author":"Mani","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1093\/jn\/nxaa129","article-title":"Dietary L-Tryptophan Regulates Colonic Serotonin Homeostasis in Mice with Dextran Sodium Sulfate-Induced Colitis","volume":"150","author":"Wang","year":"2020","journal-title":"J. Nutr."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3294","DOI":"10.1038\/s41467-018-05470-4","article-title":"Microbial tryptophan catabolites in health and disease","volume":"9","author":"Roager","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"100208","DOI":"10.1016\/j.medidd.2025.100208","article-title":"Novel indole-based synthetic molecules in cancer treatment: Synthetic strategies and structure-activity relationship","volume":"27","author":"Debnath","year":"2025","journal-title":"Med. Drug Discov."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1016\/j.cmet.2023.06.004","article-title":"Tryptophan metabolism in health and disease","volume":"35","author":"Xue","year":"2023","journal-title":"Cell Metab."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Yang, J., Wang, H., Yan, J., Sun, J., Wang, Y., Huang, G., Zhang, F., Cao, H., and Li, D. (2025). Biotherapeutic potential of gut microbiota-derived indole-3-acetic acid. Crit. Rev. Microbiol., 1\u201321.","DOI":"10.1080\/1040841X.2025.2532611"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.immuni.2013.08.003","article-title":"Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22","volume":"39","author":"Zelante","year":"2013","journal-title":"Immunity"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1038\/s41418-018-0070-2","article-title":"Lactobacillus accelerates ISCs regeneration to protect the integrity of intestinal mucosa through activation of STAT3 signaling pathway induced by LPLs secretion of IL-22","volume":"25","author":"Hou","year":"2018","journal-title":"Cell Death Differ."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.cbi.2018.04.020","article-title":"6-Formylindolo(3,2-b)carbazole induced aryl hydrocarbon receptor activation prevents intestinal barrier dysfunction through regulation of claudin-2 expression","volume":"288","author":"Ma","year":"2018","journal-title":"Chem. Biol. Interact."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1016\/j.chom.2018.05.003","article-title":"Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease","volume":"23","author":"Agus","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Joni\u0107, N., Koprivica, I., Chatzigiannis, C.M., Tsiailanis, A.D., Kyrkou, S.G., Tzakos, E.P., Pavi\u0107, A., Dimitrijevi\u0107, M., Jovanovi\u0107, A., and Jovanovi\u0107, M.B. (2024). Development of FluoAHRL: A Novel Synthetic Fluorescent Compound That Activates AHR and Potentiates Anti-Inflammatory T Regulatory Cells. Molecules, 29.","DOI":"10.3390\/molecules29132988"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Wellems, D., Hu, Y., Jennings, S., and Wang, G. (2023). Loss of CFTR function in macrophages alters the cell transcriptional program and delays lung resolution of inflammation. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1242381"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/s41579-020-0433-9","article-title":"Gut microbiota in human metabolic health and disease","volume":"19","author":"Fan","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"102262","DOI":"10.1016\/j.coph.2022.102262","article-title":"The changing landscape of the cystic fibrosis lung environment: From the perspective of Pseudomonas aeruginosa","volume":"65","author":"Greenwald","year":"2022","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"61","DOI":"10.3103\/S0891416825700077","article-title":"Complex Interplay between Biofilm Formation, Antibiotic Resistance, and Virulence in Pseudomonas aeruginosa: A Phenotypic and Genotypic Study","volume":"40","author":"Vohra","year":"2025","journal-title":"Mol. Genet. Microbiol. Virol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"eaaw1629","DOI":"10.1126\/science.aaw1629","article-title":"Host monitoring of quorum sensing during Pseudomonas aeruginosa infection","volume":"366","author":"Puyskens","year":"2019","journal-title":"Science"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"121004","DOI":"10.1016\/j.ijpharm.2021.121004","article-title":"Development and in vitro-in vivo performances of an inhalable indole-3-carboxaldehyde dry powder to target pulmonary inflammation and infection","volume":"607","author":"Puccetti","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.ccm.2016.11.014","article-title":"Respiratory Viral Infections in Chronic Lung Diseases","volume":"38","author":"Britto","year":"2017","journal-title":"Clin. Chest Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1038\/s41586-023-06287-y","article-title":"Endothelial AHR activity prevents lung barrier disruption in viral infection","volume":"621","author":"Major","year":"2023","journal-title":"Nature"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"600","DOI":"10.4049\/jimmunol.2300325","article-title":"Aryl Hydrocarbon Receptor Activation in Pulmonary Alveolar Epithelial Cells Limits Inflammation and Preserves Lung Epithelial Cell Integrity","volume":"213","author":"Zimmerman","year":"2024","journal-title":"J. Immunol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3951","DOI":"10.1007\/s11010-025-05243-w","article-title":"Chloride channels and mast cell function: Pioneering new frontiers in IBD therapy","volume":"480","author":"Aljameeli","year":"2025","journal-title":"Mol. Cell Biochem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1016\/j.jcf.2025.05.006","article-title":"Fecal microbiota changes in people with cystic fibrosis after 6 months of elexacaftor\/tezacaftor\/ivacaftor: Findings from the promise study","volume":"24","author":"Duong","year":"2025","journal-title":"J. Cyst. Fibros."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Wang, G., Fan, Y., Zhang, G., Cai, S., Ma, Y., Yang, L., Wang, Y., Yu, H., Qiao, S., and Zeng, X. (2024). Microbiota-derived indoles alleviate intestinal inflammation and modulate microbiome by microbial cross-feeding. Microbiome, 12.","DOI":"10.1186\/s40168-024-01750-y"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1038\/jid.2014.503","article-title":"The Tryptophan-Derived Endogenous Aryl Hydrocarbon Receptor Ligand 6-Formylindolo[3,2-b]Carbazole Is a Nanomolar UVA Photosensitizer in Epidermal Keratinocytes","volume":"135","author":"Park","year":"2015","journal-title":"J. Investig. Dermatol."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Liu, D., Zhang, S., Li, S., Zhang, Q., Cai, Y., Li, P., Li, H., Shen, B., Liao, Q., and Hong, Y. (2023). Indoleacrylic acid produced by Parabacteroides distasonis alleviates type 2 diabetes via activation of AhR to repair intestinal barrier. BMC Biol., 21.","DOI":"10.1186\/s12915-023-01578-2"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.prrv.2010.07.003","article-title":"Challenging and emerging pathogens in cystic fibrosis","volume":"11","author":"Wolfs","year":"2010","journal-title":"Paediatr. Respir. Rev."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2774","DOI":"10.3945\/jn.115.217406","article-title":"Dietary Sodium Butyrate Decreases Postweaning Diarrhea by Modulating Intestinal Permeability and Changing the Bacterial Communities in Weaned Piglets","volume":"145","author":"Huang","year":"2015","journal-title":"J. Nutr."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/j.jcf.2024.06.016","article-title":"Gut microbiota in adults with cystic fibrosis: Implications for the severity of the CFTR gene mutation and nutritional status","volume":"23","author":"Mazurkiewicz","year":"2024","journal-title":"J. Cyst. Fibros."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/s41591-019-0714-x","article-title":"Fecal dysbiosis in infants with cystic fibrosis is associated with early linear growth failure","volume":"26","author":"Hayden","year":"2020","journal-title":"Nat. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1080\/10408398.2019.1598334","article-title":"Tryptophan (Trp) modulates gut homeostasis via aryl hydrocarbon receptor (AhR)","volume":"60","author":"Sun","year":"2020","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Lu, H., Zhang, G., Wang, K., Liu, K., Gao, Y., Chen, J., Li, Y., and Yan, J. (2025). The Role of Lactiplantibacillus plantarum CGMCC9513 in Alleviating Colitis by Synergistic Enhancement of the Intestinal Barrier Through Modulating Gut Microbiota and Activating the Aryl Hydrocarbon Receptor. Probiotics Antimicrob Proteins, 1\u201313.","DOI":"10.1007\/s12602-025-10551-0"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"eadk9145","DOI":"10.1126\/scitranslmed.adk9145","article-title":"Perinatal dysfunction of innate immunity in cystic fibrosis","volume":"17","author":"Jaudas","year":"2025","journal-title":"Sci. Transl. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"L530","DOI":"10.1152\/ajplung.00621.2020","article-title":"CF monocyte-derived macrophages have an attenuated response to extracellular vesicles secreted by airway epithelial cells","volume":"320","author":"Koeppen","year":"2021","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1016\/j.immuni.2017.08.016","article-title":"Aryl Hydrocarbon Receptor Controls Monocyte Differentiation into Dendritic Cells versus Macrophages","volume":"47","author":"Goudot","year":"2017","journal-title":"Immunity"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1007\/s11418-021-01506-0","article-title":"Indole-3-carboxaldehyde regulates RSV-induced inflammatory response in RAW264.7 cells by moderate inhibition of the TLR7 signaling pathway","volume":"75","author":"Hou","year":"2021","journal-title":"J. Nat. Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1128\/JB.01477-10","article-title":"Indole transport across Escherichia coli membranes","volume":"193","author":"Chimerel","year":"2011","journal-title":"J. Bacteriol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.apsb.2024.11.009","article-title":"Gut microbiota-derived tryptophan metabolites regulated by Wuji Wan to attenuate colitis through AhR signaling activation","volume":"15","author":"Jing","year":"2025","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1021\/acs.jafc.0c05205","article-title":"Indole-3-propionic Acid Improved the Intestinal Barrier by Enhancing Epithelial Barrier and Mucus Barrier","volume":"69","author":"Li","year":"2021","journal-title":"J. Agric. Food Chem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2467235","DOI":"10.1080\/19490976.2025.2467235","article-title":"Microbiota-derived IPA alleviates intestinal mucosal inflammation through upregulating Th1\/Th17 cell apoptosis in inflammatory bowel disease","volume":"17","author":"Gao","year":"2025","journal-title":"Gut Microbes"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Munakarmi, S., Chand, L., Shin, H.B., Jang, K.Y., and Jeong, Y.J. (2020). Indole-3-Carbinol Derivative DIM Mitigates Carbon Tetrachloride-Induced Acute Liver Injury in Mice by Inhibiting Inflammatory Response, Apoptosis and Regulating Oxidative Stress. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21062048"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Fu, Y., Gao, H., Hou, X., Chen, Y., and Xu, K. (2022). Pretreatment with IPA ameliorates colitis in mice: Colon transcriptome and fecal 16S amplicon profiling. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1014881"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.jnutbio.2017.11.011","article-title":"Preventive effects of indole-3-carbinol against alcohol-induced liver injury in mice via antioxidant, anti-inflammatory, and anti-apoptotic mechanisms: Role of gut-liver-adipose tissue axis","volume":"55","author":"Choi","year":"2018","journal-title":"J. Nutr. Biochem."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Puccetti, M., Pariano, M., Renga, G., Santarelli, I., D\u2019Onofrio, F., Bellet, M.M., Stincardini, C., Bartoli, A., Costantini, C., and Romani, L. (2021). Targeted Drug Delivery Technologies Potentiate the Overall Therapeutic Efficacy of an Indole Derivative in a Mouse Cystic Fibrosis Setting. Cells, 10.","DOI":"10.3390\/cells10071601"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"RP87458","DOI":"10.7554\/eLife.87458","article-title":"Oral supplementation of gut microbial metabolite indole-3-acetate alleviates diet-induced steatosis and inflammation in mice","volume":"12","author":"Ding","year":"2024","journal-title":"eLife"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.chom.2017.06.007","article-title":"Indoleacrylic Acid Produced by Commensal Peptostreptococcus Species Suppresses Inflammation","volume":"22","author":"Wlodarska","year":"2017","journal-title":"Cell Host Microbe"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.freeradbiomed.2014.06.003","article-title":"Scavenging of reactive oxygen species by tryptophan metabolites helps Pseudomonas aeruginosa escape neutrophil killing","volume":"73","author":"Genestet","year":"2014","journal-title":"Free Radic. Biol. Med."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"119733","DOI":"10.1016\/j.cca.2024.119733","article-title":"Exhaled breath analysis in adult patients with cystic fibrosis by real-time proton mass spectrometry","volume":"560","author":"Mustafina","year":"2024","journal-title":"Clin. Chim. Acta"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Mustafina, M., Silantyev, A., Krasovskiy, S., Chernyak, A., Naumenko, Z., Suvorov, A., Gognieva, D., Abdullaev, M., Suvorova, O., and Schmidt, A. (2024). Identification of Exhaled Metabolites Correlated with Respiratory Function and Clinical Features in Adult Patients with Cystic Fibrosis by Real-Time Proton Mass Spectrometry. Biomolecules, 14.","DOI":"10.3390\/biom14091189"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Puccetti, M., Pariano, M., Wojtylo, P., Schoubben, A., Giovagnoli, S., and Ricci, M. (2023). Turning Microbial AhR Agonists into Therapeutic Agents via Drug Delivery Systems. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15020506"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"G687","DOI":"10.1152\/ajpgi.00306.2023","article-title":"Oral tryptophan activates duodenal aryl hydrocarbon receptor in healthy subjects: A crossover randomized controlled trial","volume":"326","author":"Rueda","year":"2024","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1039\/D3MD00677H","article-title":"Indole-containing pharmaceuticals: Targets, pharmacological activities, and SAR studies","volume":"15","author":"Zeng","year":"2024","journal-title":"RSC Med. Chem."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.cell.2021.12.009","article-title":"Mechanism of CFTR correction by type I folding correctors","volume":"185","author":"Fiedorczuk","year":"2022","journal-title":"Cell"},{"key":"ref_101","unstructured":"Ruah, S.S.H., Grootenhuis, P.D., Van Goor, F., Zhou, J., Bear, B., Miller, M.T., Numa, M.M.D., and Yang, X. (2025). Indole Derivatives as CFTR Modulators. (No. 7,645,789), U.S. Patent."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"112888","DOI":"10.1016\/j.ejmech.2020.112888","article-title":"1-BENZYLSPIRO[PIPERIDINE-4,1\u2032-PYRIDO[3,4-b]indole] \u2018co-potentiators\u2019 for minimal function CFTR mutants","volume":"209","author":"Son","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"11169","DOI":"10.1021\/acs.jmedchem.0c01050","article-title":"Identification, Structure-Activity Relationship, and Biological Characterization of 2,3,4,5-Tetrahydro-1H-pyrido[4,3-b]indoles as a Novel Class of CFTR Potentiators","volume":"63","author":"Brindani","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1016\/j.cell.2020.07.038","article-title":"IL4I1 Is a Metabolic Immune Checkpoint that Activates the AHR and Promotes Tumor Progression","volume":"182","author":"Sadik","year":"2020","journal-title":"Cell"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Chen, L.B., Zhu, S.P., Liu, T.P., Zhao, H., Chen, P.F., Duan, Y.J., and Hu, R. (2021). Cancer Associated Fibroblasts Promote Renal Cancer Progression Through a TDO\/Kyn\/AhR Dependent Signaling Pathway. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.628821"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"131262","DOI":"10.1016\/j.jhazmat.2023.131262","article-title":"Role of macrophage AHR\/TLR4\/STAT3 signaling axis in the colitis induced by non-canonical AHR ligand aflatoxin B1","volume":"452","author":"Zhang","year":"2023","journal-title":"J. Hazard. Mater."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"107909","DOI":"10.1016\/j.phrs.2025.107909","article-title":"The aryl hydrocarbon receptor: A promising target for intestinal fibrosis therapy","volume":"219","author":"Pan","year":"2025","journal-title":"Pharmacol. Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"134560","DOI":"10.1016\/j.jhazmat.2024.134560","article-title":"Benzo[a]pyrene evokes epithelial-mesenchymal transition and pulmonary fibrosis through AhR-mediated Nrf2-p62 signaling","volume":"473","author":"Li","year":"2024","journal-title":"J. Hazard. Mater."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"109255","DOI":"10.1016\/j.intimp.2022.109255","article-title":"Ameliorative effect of the probiotic peptide against benzo(\u03b1)pyrene-induced inflammatory damages in enterocytes","volume":"112","author":"Luo","year":"2022","journal-title":"Int. Immunopharmacol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"e2402066","DOI":"10.1002\/advs.202402066","article-title":"Uremic Toxin Receptor AhR Facilitates Renal Senescence and Fibrosis via Suppressing Mitochondrial Biogenesis","volume":"11","author":"Xie","year":"2024","journal-title":"Adv. Sci."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.bcp.2016.08.021","article-title":"The antiandrogen flutamide is a novel aryl hydrocarbon receptor ligand that disrupts bile acid homeostasis in mice through induction of Abcc4","volume":"119","author":"Gao","year":"2016","journal-title":"Biochem. Pharmacol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/s00109-023-02289-5","article-title":"Activation of aryl hydrocarbon receptor (AhR) in Alzheimer\u2019s disease: Role of tryptophan metabolites generated by gut host-microbiota","volume":"101","author":"Salminen","year":"2023","journal-title":"J. Mol. Med."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/j.kint.2019.09.029","article-title":"Temporal and tissue-specific activation of aryl hydrocarbon receptor in discrete mouse models of kidney disease","volume":"97","author":"Walker","year":"2020","journal-title":"Kidney Int."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Tanaka, M., Fujikawa, M., Oguro, A., Itoh, K., Vogel, C.F.A., and Ishihara, Y. (2021). Involvement of the Microglial Aryl Hydrocarbon Receptor in Neuroinflammation and Vasogenic Edema after Ischemic Stroke. Cells, 10.","DOI":"10.3390\/cells10040718"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"5652","DOI":"10.1073\/pnas.1037886100","article-title":"Distinct response to dioxin in an arylhydrocarbon receptor (AHR)-humanized mouse","volume":"100","author":"Moriguchi","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"123261","DOI":"10.1016\/j.envpol.2023.123261","article-title":"Combined exposure of MAHs and PAHs enhanced amino acid and lipid metabolism disruption in epithelium leading asthma risk","volume":"343","author":"Shen","year":"2024","journal-title":"Environ. Pollut."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"5467","DOI":"10.2147\/OTT.S194870","article-title":"Comparative review of drug-drug interactions with epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of non-small-cell lung cancer","volume":"12","author":"Xu","year":"2019","journal-title":"Onco Targets Ther."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"7326","DOI":"10.1021\/acs.jmedchem.0c00506","article-title":"Discovery of Novel Indole-Based Allosteric Highly Potent ATX Inhibitors with Great In Vivo Efficacy in a Mouse Lung Fibrosis Model","volume":"63","author":"Lei","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_119","first-page":"329","article-title":"Advanced nanotherapies for precision treatment of inflammatory lung diseases","volume":"53","author":"Qi","year":"2025","journal-title":"Bioact. Mater."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1007\/s11696-021-01921-3","article-title":"Fabrication and in vitro\/in vivo characterization of Eudragit enteric nanoparticles loaded with indomethacin","volume":"76","author":"Wang","year":"2022","journal-title":"Chem. Pap."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/20\/9876\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:34:32Z","timestamp":1760114072000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/20\/9876"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,10]]},"references-count":120,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["ijms26209876"],"URL":"https:\/\/doi.org\/10.3390\/ijms26209876","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,10]]}}}