{"doi":"10.1073/pnas.2204557119","title":"The aryl hydrocarbon receptor instructs the immunomodulatory profile of a subset of Clec4a4 <sup>+</sup> eosinophils unique to the small intestine","abstract":"C-type lectin domain family 4, member a4 (Clec4a4) is a C-type lectin inhibitory receptor specific for glycans thought to be exclusively expressed on murine CD8α− conventional dendritic cells. Using newly generated Clec4a4-mCherry knock-in mice, we identify a subset of Clec4a4-expressing eosinophils uniquely localized in the small intestine lamina propria. Clec4a4+ eosinophils evinced an immunomodulatory signature, whereas Clec4a4− eosinophils manifested a proinflammatory profile. Clec4a4+ eosinophils expressed high levels of aryl hydrocarbon receptor (Ahr), which drove the expression of Clec4a4 as well as other immunomodulatory features, such as PD-L1. The abundance of Clec4a4+ eosinophils was dependent on dietary AHR ligands, increased with aging, and declined in inflammatory conditions. Mice lacking AHR in eosinophils expanded innate lymphoid cells of type 2 and cleared Nippostrongylus brasiliensis infection more effectively than did wild-type mice. These results highlight the heterogeneity of eosinophils in response to tissue cues and identify a unique AHR-dependent subset of eosinophils in the small intestine with an immunomodulatory profile.","journal":"Proceedings of the National Academy of Sciences","year":2022,"id":244557,"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":28,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9516,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":878279,"name":"Jun Kasamatsu","orcid":"0000-0001-9718-8377","position":1,"is_corresponding":false},{"id":634230,"name":"Satoru Joshita","orcid":"0000-0002-6364-9654","position":2,"is_corresponding":false},{"id":109979,"name":"Susan Gilfillan","orcid":"0000-0003-1672-0996","position":3,"is_corresponding":false},{"id":314945,"name":"Blanda Di Luccia","orcid":"0000-0002-0137-953X","position":4,"is_corresponding":false},{"id":878985,"name":"Santosh K. Panda","orcid":null,"position":5,"is_corresponding":false},{"id":495207,"name":"DoHyun Kim","orcid":"0000-0002-4840-355X","position":6,"is_corresponding":false},{"id":652105,"name":"Pritesh Desai","orcid":"0000-0002-4697-9475","position":7,"is_corresponding":false},{"id":249173,"name":"Jennifer K. Bando","orcid":"0000-0002-1331-7424","position":8,"is_corresponding":false},{"id":623228,"name":"Stanley Ching‐Cheng Huang","orcid":"0000-0002-6557-3737","position":9,"is_corresponding":false},{"id":878280,"name":"Kentaro Yomogida","orcid":"0000-0003-4171-6606","position":10,"is_corresponding":false},{"id":878281,"name":"Hitomi Hoshino","orcid":"0000-0002-4522-3190","position":11,"is_corresponding":false},{"id":878986,"name":"Mana Fukushima","orcid":null,"position":12,"is_corresponding":false},{"id":287793,"name":"Elizabeth A. Jacobsen","orcid":"0000-0003-2956-753X","position":13,"is_corresponding":false},{"id":478432,"name":"Steven J. Van Dyken","orcid":"0000-0002-9787-0883","position":14,"is_corresponding":false},{"id":878282,"name":"Christiane Ruedl","orcid":"0000-0002-5599-6541","position":15,"is_corresponding":false},{"id":109978,"name":"Marina Cella","orcid":"0000-0003-1230-1313","position":16,"is_corresponding":false},{"id":71132,"name":"Marco Colonna","orcid":"0000-0001-5222-4987","position":17,"is_corresponding":false},{"id":878278,"name":"Wei-Le Wang","orcid":"0000-0002-6984-4514","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-19T00:23:30.364338Z","pmid":"35653568","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":[]}