{"doi":"10.1002/jlb.1a0420-012rr","title":"Trophoblast-secreted soluble-PD-L1 modulates macrophage polarization and function","abstract":"Abstract Decidual macrophages are in close contact with trophoblast cells during placenta development, and an appropriate crosstalk between these cellular compartments is crucial for the establishment and maintenance of a healthy pregnancy. During different phases of gestation, macrophages undergo dynamic changes to adjust to the different stages of fetal development. Trophoblast-secreted factors are considered the main modulators responsible for macrophage differentiation and function. However, the phenotype of these macrophages induced by trophoblast-secreted factors and the factors responsible for their polarization has not been elucidated. In this study, we characterized the phenotype and function of human trophoblast-induced macrophages. Using in vitro models, we found that human trophoblast-educated macrophages were CD14+CD206+CD86− and presented an unusual transcriptional profile in response to TLR4/LPS activation characterized by the expression of type I IFN-β expression. IFN-β further enhances the constitutive production of soluble programmed cell death ligand 1 (PD-L1) from trophoblast cells. PD-1 blockage inhibited trophoblast-induced macrophage differentiation. Soluble PD-L1 (sPD-L1) was detected in the blood of pregnant women and increased throughout the gestation. Collectively, our data suggest the existence of a regulatory circuit at the maternal fetal interface wherein IFN-β promotes sPD-L1 expression/secretion by trophoblast cells, which can then initiate a PD-L1/PD-1-mediated macrophage polarization toward an M2 phenotype, consequently decreasing inflammation. Macrophages then maintain the expression of sPD-L1 by the trophoblasts through IFN-β production induced through TLR4 ligation.","journal":"Journal of Leukocyte Biology","year":2020,"id":64949,"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":68,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9512,"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":343665,"name":"Paulomi Aldo","orcid":null,"position":1,"is_corresponding":false},{"id":342963,"name":"Yuan You","orcid":"0000-0001-5364-5185","position":2,"is_corresponding":false},{"id":322785,"name":"Jiahui Ding","orcid":"0000-0001-7747-2071","position":3,"is_corresponding":false},{"id":342964,"name":"Janina Kaislasuo","orcid":"0000-0003-4399-3906","position":4,"is_corresponding":false},{"id":342965,"name":"Jesper Friis Petersen","orcid":"0000-0002-5619-1809","position":5,"is_corresponding":false},{"id":342966,"name":"Ellen Løkkegaard","orcid":"0000-0003-4149-5663","position":6,"is_corresponding":false},{"id":326594,"name":"Gang Peng","orcid":"0000-0003-0307-9351","position":7,"is_corresponding":false},{"id":342967,"name":"Michael J. Paidas","orcid":"0000-0001-5561-7196","position":8,"is_corresponding":false},{"id":342968,"name":"Samantha Simpson","orcid":"0000-0002-4610-8530","position":9,"is_corresponding":false},{"id":270482,"name":"Lubna Pal","orcid":"0000-0002-9900-9392","position":10,"is_corresponding":false},{"id":342969,"name":"Seth Guller","orcid":"0000-0003-0651-8241","position":11,"is_corresponding":false},{"id":342970,"name":"Hong Liu","orcid":"0000-0002-3464-1418","position":12,"is_corresponding":false},{"id":343666,"name":"Ai Hua Liao","orcid":null,"position":13,"is_corresponding":false},{"id":322789,"name":"Gil Mor","orcid":"0000-0002-5499-3912","position":14,"is_corresponding":false},{"id":342962,"name":"Yonghong Zhang","orcid":"0000-0001-6188-3490","position":0,"is_corresponding":true}],"reference_count":85,"raw_metadata":null,"created_at":"2026-07-18T21:12:58.081635Z","pmid":"32386458","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":[]}