{"doi":"10.1126/sciadv.aay8230","title":"Modulation of lymphocyte-mediated tissue repair by rational design of heterocyclic aryl hydrocarbon receptor agonists","abstract":"Aryl hydrocarbon receptor (AHR) is an essential regulator of gut immunity and a promising therapeutic target for inflammatory bowel disease (IBD). Current AHR agonists are inadequate for clinical translation due to low activity, inadequate pharmacokinetics, or toxicity. We synthesized a structurally diverse library and used integrated computational and experimental studies to discover mechanisms governing ligand-receptor interaction and to design potent drug leads PY109 and PY108, which display physiochemical drug-likeness properties, desirable pharmacokinetic profiles, and low toxicity. In a murine model of dextran sulfate sodium-induced colitis, orally administered compounds increase interleukin-22 (IL-22) production and accelerate mucosal healing by modulating mucosal adaptive and innate lymphoid cells. AHR and IL-22 pathway induction was confirmed using RNA sequencing and characterization of the lymphocyte protein-protein interaction network. Significant induction of IL-22 was also observed using human T cells from patients with IBD. Our findings support rationally designed AHR agonists for IBD therapy.","journal":"Science Advances","year":2020,"id":65710,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":55,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9563,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":347944,"name":"Carolyn A. Haller","orcid":"0000-0003-1963-3695","position":1,"is_corresponding":false},{"id":347945,"name":"Finith E. Jernigan","orcid":"0000-0001-8093-4708","position":2,"is_corresponding":false},{"id":347946,"name":"Steffi Koerner","orcid":"0000-0003-2635-6796","position":3,"is_corresponding":false},{"id":347947,"name":"Daniel J. Wong","orcid":"0000-0002-7093-3397","position":4,"is_corresponding":false},{"id":347948,"name":"Yiqiang Wang","orcid":"0000-0003-1552-7529","position":5,"is_corresponding":false},{"id":347949,"name":"Jae Eun Cheong","orcid":"0000-0001-7585-5570","position":6,"is_corresponding":false},{"id":1231,"name":"Revanth Kosaraju","orcid":null,"position":7,"is_corresponding":false},{"id":253650,"name":"Julian Kwan","orcid":"0000-0002-9199-1828","position":8,"is_corresponding":false},{"id":281708,"name":"Dayoung Park","orcid":"0000-0003-4983-4340","position":9,"is_corresponding":false},{"id":347950,"name":"Beena Thomas","orcid":"0000-0002-0047-6223","position":10,"is_corresponding":false},{"id":253630,"name":"Swati S. Bhasin","orcid":"0000-0001-8661-1459","position":11,"is_corresponding":false},{"id":347951,"name":"Roberto C. De La Rosa","orcid":"0000-0002-0020-2150","position":12,"is_corresponding":false},{"id":347952,"name":"Alykhan Premji","orcid":"0000-0002-0326-3717","position":13,"is_corresponding":false},{"id":347953,"name":"Liying Liu","orcid":"0000-0001-8560-3035","position":14,"is_corresponding":false},{"id":349473,"name":"Eden Park","orcid":null,"position":15,"is_corresponding":false},{"id":347954,"name":"Alan C. Moss","orcid":"0000-0003-0179-5477","position":16,"is_corresponding":false},{"id":253656,"name":"Andrew Emili","orcid":"0000-0001-8995-246X","position":17,"is_corresponding":false},{"id":253631,"name":"Manoj Bhasin","orcid":"0000-0001-5172-420X","position":18,"is_corresponding":false},{"id":347955,"name":"Lijun Sun","orcid":"0000-0002-1579-2253","position":19,"is_corresponding":false},{"id":347956,"name":"Elliot L. Chaikof","orcid":"0000-0001-6184-4571","position":20,"is_corresponding":false},{"id":347943,"name":"Jiaxuan Chen","orcid":"0000-0001-5801-9052","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-18T21:13:43.728351Z","pmid":"31998845","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}