{"doi":"10.4049/jimmunol.2100439","title":"IL-22 Plays a Dual Role in the Amniotic Cavity: Tissue Injury and Host Defense against Microbes in Preterm Labor","abstract":"Abstract IL-22 is a multifaceted cytokine with both pro- and anti-inflammatory functions that is implicated in multiple pathologies. However, the role of IL-22 in maternal-fetal immunity in late gestation is poorly understood. In this study, we first showed that IL-22+ T cells coexpressing retinoic acid–related orphan receptor γt (ROR-γt) are enriched at the human maternal-fetal interface of women with preterm labor and birth, which was confirmed by in silico analysis of single-cell RNA sequencing data. T cell activation leading to preterm birth in mice was preceded by a surge in IL-22 in the maternal circulation and amniotic cavity; however, systemic administration of IL-22 in mice did not induce adverse perinatal outcomes. Next, using an ex vivo human system, we showed that IL-22 can cross from the choriodecidua to the intra-amniotic space, where its receptors (Il22ra1, Il10rb, and Il22ra2) are highly expressed by murine gestational and fetal tissues in late pregnancy. Importantly, amniotic fluid concentrations of IL-22 were elevated in women with sterile or microbial intra-amniotic inflammation, suggesting a dual role for this cytokine. The intra-amniotic administration of IL-22 alone shortened gestation and caused neonatal death in mice, with the latter outcome involving lung maturation and inflammation. IL-22 plays a role in host response by participating in the intra-amniotic inflammatory milieu preceding Ureaplasma parvum–induced preterm birth in mice, which was rescued by the deficiency of IL-22. Collectively, these data show that IL-22 alone is capable of causing fetal injury leading to neonatal death and can participate in host defense against microbial invasion of the amniotic cavity leading to preterm labor and birth.","journal":"The Journal of Immunology","year":2022,"id":253261,"datarank":0.47032413238937254,"base_score":3.1354942159291497,"endowment":3.1354942159291497,"self_citation_contribution":0.47032413238937254,"citation_network_contribution":0.0,"self_endowment_contribution":0.47032413238937254,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":22,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9552,"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":236857,"name":"Roberto Romero","orcid":"0000-0002-4448-5121","position":1,"is_corresponding":false},{"id":275419,"name":"Marcia Arenas‐Hernandez","orcid":"0000-0002-1178-6112","position":2,"is_corresponding":false},{"id":275422,"name":"José Galaz","orcid":"0000-0002-8160-8581","position":3,"is_corresponding":false},{"id":349020,"name":"Kenichiro Motomura","orcid":"0000-0003-1519-5501","position":4,"is_corresponding":false},{"id":586126,"name":"Tao Li","orcid":"0000-0003-1531-358X","position":5,"is_corresponding":false},{"id":120720,"name":"Yi Xu","orcid":"0000-0001-8894-525X","position":6,"is_corresponding":false},{"id":275420,"name":"Derek Miller","orcid":"0000-0002-5812-7771","position":7,"is_corresponding":false},{"id":65311,"name":"Roger Piqué-Regi","orcid":"0000-0002-1262-2275","position":8,"is_corresponding":false},{"id":898708,"name":"Gregorio Martinez","orcid":"0000-0003-0099-1505","position":9,"is_corresponding":false},{"id":898709,"name":"Yesong Liu","orcid":"0000-0003-0951-4692","position":10,"is_corresponding":false},{"id":240935,"name":"Eunjung Jung","orcid":"0000-0003-0897-0039","position":11,"is_corresponding":false},{"id":243682,"name":"Robert Para","orcid":null,"position":12,"is_corresponding":false},{"id":236861,"name":"Nardhy Gomez‐Lopez","orcid":"0000-0002-3406-5262","position":13,"is_corresponding":false},{"id":633479,"name":"Meyer Gershater","orcid":null,"position":0,"is_corresponding":true}],"reference_count":196,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:24:55.325369Z","pmid":"35304419","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":[]}