{"doi":"10.1101/2023.09.25.559429","title":"Activation of the aryl hydrocarbon receptor inhibits neuropilin-1 upregulation on IL-2 responding CD4 <sup>+</sup> T cells","abstract":"Abstract Neuropilin-1 (Nrp1), a transmembrane protein expressed on CD4 + T cells, is mostly studied in the context of regulatory T cell (Treg) function. More recently, there is increasing evidence that Nrp1 is also highly expressed on activated effector T cells and that increases in these Nrp1-expressing CD4 + T cells correspond with immunopathology across several T cell-dependent disease models. Thus, Nrp1 may be implicated in the identification and function of immunopathologic T cells. Nrp1 downregulation in CD4 + T cells is one of the strongest transcriptional changes in response to immunoregulatory compounds that act though the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor. To better understand the link between AhR and Nrp1 expression on CD4 + T cells, Nrp1 expression was assessed in vivo and in vitro following AhR ligand treatment. In the current study, we identified that the percentage of Nrp1 expressing CD4 + T cells increases over the course of activation and proliferation in vivo . The actively dividing Nrp1 + Foxp3 - cells express the classic effector phenotype of CD44 hi CD45RB lo , and the increase in Nrp1 + Foxp3 - cells is prevented by AhR activation. In contrast, Nrp1 expression is not modulated by AhR activation in non-proliferating CD4 + T cells. The downregulation of Nrp1 on CD4 + T cells was recapitulated in vitro in cells isolated from C57BL/6 and NOD (non-obese diabetic) mice. CD4 + Foxp3 - cells expressing CD25, stimulated with IL-2, or differentiated into Th1 cells, were particularly sensitive to AhR-mediated inhibition of Nrp1 upregulation. IL-2 was necessary for AhR-dependent downregulation of Nrp1 expression both in vitro and in vivo . Collectively, the data demonstrate that Nrp1 is a CD4 + T cell activation marker and that regulation of Nrp1 could be a previously undescribed mechanism by which AhR ligands modulate effector CD4 + T cell responses.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":411960,"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":0,"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":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1192502,"name":"Keegan Malany","orcid":"0000-0002-4775-2440","position":1,"is_corresponding":false},{"id":738218,"name":"Krista Thongphanh","orcid":"0000-0003-0167-3306","position":2,"is_corresponding":false},{"id":525552,"name":"Clarisa Martinez","orcid":"0000-0001-8529-0016","position":3,"is_corresponding":false},{"id":235507,"name":"Michael L. Goodson","orcid":"0000-0002-3464-490X","position":4,"is_corresponding":false},{"id":839124,"name":"Felipe da Costa Souza","orcid":"0000-0001-9718-4800","position":5,"is_corresponding":false},{"id":782460,"name":"Lo-Wei Lin","orcid":"0000-0002-0876-7826","position":6,"is_corresponding":false},{"id":714646,"name":"Jamie M. Pennington","orcid":null,"position":7,"is_corresponding":false},{"id":227733,"name":"Pamela J. Lein","orcid":"0000-0001-7665-7584","position":8,"is_corresponding":false},{"id":1192503,"name":"Nancy Kerkvliet","orcid":"0000-0003-2777-7947","position":9,"is_corresponding":false},{"id":1192504,"name":"Allison Ehrlich","orcid":"0000-0002-0994-6471","position":10,"is_corresponding":false},{"id":1192924,"name":"Simone Sandoval","orcid":null,"position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-19T01:21:46.548301Z","pmid":"37808764","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":[]}