{"doi":"10.1172/jci.insight.139965","title":"Stem cell transplantation uncovers TDO-AHR regulation of lung dendritic cells in herpesvirus-induced pathology","abstract":"The aryl-hydrocarbon receptor (AHR) is an intracellular sensor of aromatic hydrocarbons that sits at the top of various immunomodulatory pathways. Here, we present evidence that AHR plays a role in controlling IL-17 responses and the development of pulmonary fibrosis in response to respiratory pathogens following bone marrow transplant (BMT). Mice infected intranasally with gamma-herpesvirus 68 (γHV-68) following BMT displayed elevated levels of the AHR ligand, kynurenine (kyn), in comparison with control mice. Inhibition or genetic ablation of AHR signaling resulted in a significant decrease in IL-17 expression as well as a reduction in lung pathology. Lung CD103+ DCs expressed AHR following BMT, and treatment of induced CD103+ DCs with kyn resulted in altered cytokine production in response to γHV-68. Interestingly, mice deficient in the kyn-producing enzyme indolamine 2-3 dioxygenase showed no differences in cytokine responses to γHV-68 following BMT; however, isolated pulmonary fibroblasts infected with γHV-68 expressed the kyn-producing enzyme tryptophan dioxygenase (TDO2). Our data indicate that alterations in the production of AHR ligands in response to respiratory pathogens following BMT results in a pro-Th17 phenotype that drives lung pathology. We have further identified the TDO2/AHR axis as a potentially novel form of intercellular communication between fibroblasts and DCs that shapes immune responses to respiratory pathogens.","journal":"JCI Insight","year":2021,"id":188841,"datarank":0.41588830833596724,"base_score":2.772588722239781,"endowment":2.772588722239781,"self_citation_contribution":0.41588830833596724,"citation_network_contribution":0.0,"self_endowment_contribution":0.41588830833596724,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9648,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":750697,"name":"Nicolas L. Pereira","orcid":"0000-0003-3654-4029","position":1,"is_corresponding":false},{"id":640754,"name":"Steven Hrycaj","orcid":"0000-0002-3760-1948","position":2,"is_corresponding":false},{"id":296748,"name":"Carol A. Wilke","orcid":null,"position":3,"is_corresponding":false},{"id":262125,"name":"Rachel L. Zemans","orcid":"0000-0003-3537-9869","position":4,"is_corresponding":false},{"id":277952,"name":"Bethany B. Moore","orcid":"0000-0003-3051-745X","position":5,"is_corresponding":false},{"id":406625,"name":"Stephen J. Gurczynski","orcid":"0000-0002-4238-030X","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:49:14.547082Z","pmid":"33491663","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":[]}