{"doi":"10.1084/jem.20242307","title":"Lung tissue–resident memory T cells optimize protection by IL-10 regulation of innate immunity","abstract":"Respiratory viral infections establish tissue-resident memory T cells (TRM) in the lung, which provide optimal protection against subsequent infections, though the underlying mechanisms are incompletely understood. Here, we demonstrate in a mouse model of heterosubtypic influenza infection that lung TRM attenuate inflammation by macrophages during secondary versus primary responses, in part, through production of the immunoregulatory cytokine IL-10. During secondary infections, lung TRM were the predominant producers of early IL-10; inhibiting early IL-10 signaling resulted in increased macrophage-mediated inflammation, morbidity, and lung pathology. Moreover, lung TRM were shown to directly modulate lung macrophage responses and polarization in depletion experiments. Finally, IL-10 enhanced IFN-γ production by lung memory CD8+ T cells. Human influenza-specific TRM isolated from lungs recapitulated robust IL-10 expression associated with augmented effector responses of murine TRM. These data support a dual role of TRM in coordinating in situ secondary responses-augmenting effector responses for robust viral clearance while dampening inflammation to limit tissue damage.","journal":"The Journal of Experimental Medicine","year":2025,"id":515268,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9469,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":225931,"name":"Julia Davis‐Porada","orcid":"0000-0001-9313-4590","position":1,"is_corresponding":false},{"id":327199,"name":"Daniel H. Paik","orcid":"0000-0002-6644-4742","position":2,"is_corresponding":false},{"id":1213348,"name":"Alex George","orcid":"0000-0001-6813-5241","position":3,"is_corresponding":false},{"id":353041,"name":"Brea K. Hampton","orcid":"0000-0001-7167-5652","position":4,"is_corresponding":false},{"id":1380094,"name":"Paige L. Ruschke","orcid":null,"position":5,"is_corresponding":false},{"id":225061,"name":"Peter A. Sims","orcid":"0000-0002-3921-4837","position":6,"is_corresponding":false},{"id":747864,"name":"Ziv Frankenstein","orcid":null,"position":7,"is_corresponding":false},{"id":553716,"name":"Anjali Saqi","orcid":"0000-0003-3133-9886","position":8,"is_corresponding":false},{"id":225941,"name":"Donna L. Färber","orcid":"0000-0001-8236-9183","position":9,"is_corresponding":false},{"id":1380093,"name":"An-Ya Yang","orcid":null,"position":0,"is_corresponding":true}],"reference_count":89,"raw_metadata":null,"created_at":"2026-07-19T02:48:39.436300Z","pmid":"41081716","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":[]}