{"doi":"10.1126/sciimmunol.add4132","title":"pDC-like cells are pre-DC2 and require KLF4 to control homeostatic CD4 T cells","abstract":"Plasmacytoid dendritic cells (pDCs) have been shown to play an important role during immune responses, ranging from initial viral control through the production of type I interferons to antigen presentation. However, recent studies uncovered unexpected heterogeneity among pDCs. We identified a previously uncharacterized immune subset, referred to as pDC-like cells, that not only resembles pDCs but also shares conventional DC (cDC) features. We show that this subset is a circulating precursor distinct from common DC progenitors, with prominent cDC2 potential. Our findings from human CD2-iCre and CD300c-iCre lineage tracing mouse models suggest that a substantial fraction of cDC2s originates from pDC-like cells, which can therefore be referred to as pre-DC2. This precursor subset responds to homeostatic cytokines, such as macrophage colony stimulating factor, by expanding and differentiating into cDC2 that efficiently prime T helper 17 (T H 17) cells. Development of pre-DC2 into CX3CR1 + ESAM − cDC2b but not CX3CR1 − ESAM + cDC2a requires the transcription factor KLF4. Last, we show that, under homeostatic conditions, this developmental pathway regulates the immune threshold at barrier sites by controlling the pool of T H 17 cells within skin-draining lymph nodes.","journal":"Science Immunology","year":2023,"id":316912,"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":88,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9467,"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":1021407,"name":"Athanasios Kouklas","orcid":"0000-0002-3282-0674","position":1,"is_corresponding":false},{"id":883289,"name":"Grozdan Cvijetic","orcid":"0000-0002-3263-0598","position":2,"is_corresponding":false},{"id":235854,"name":"Nicolas Bouladoux","orcid":"0000-0003-1593-671X","position":3,"is_corresponding":false},{"id":1021957,"name":"Mladen Mitrovic","orcid":null,"position":4,"is_corresponding":false},{"id":231233,"name":"Jigar V. Desai","orcid":"0000-0002-8823-0796","position":5,"is_corresponding":false},{"id":621633,"name":"Djalma S. Lima‐Junior","orcid":"0000-0002-2092-8047","position":6,"is_corresponding":false},{"id":104225,"name":"Michail S. Lionakis","orcid":"0000-0003-4994-9500","position":7,"is_corresponding":false},{"id":225267,"name":"Yasmine Belkaid","orcid":"0000-0001-9962-3571","position":8,"is_corresponding":false},{"id":1021408,"name":"Robert Ivánek","orcid":"0000-0002-8403-056X","position":9,"is_corresponding":false},{"id":445304,"name":"Roxane Tussiwand","orcid":"0000-0002-1712-868X","position":10,"is_corresponding":false},{"id":478921,"name":"Patrick Fernandes Rodrigues","orcid":"0000-0002-0214-0627","position":0,"is_corresponding":true}],"reference_count":85,"raw_metadata":null,"created_at":"2026-07-19T01:06:44.698773Z","pmid":"36827419","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":[]}