{"doi":"10.1093/jimmun/vkaf221","title":"Tristetraprolin protects against ozone-induced acute lung injury and inflammation in mice","abstract":"Tristetraprolin (TTP) is an anti-inflammatory protein that mediates messenger RNA (mRNA) decay of certain transcripts, especially those encoding proinflammatory cytokines. TTP modulates various pathological outcomes in diverse inflammatory diseases; however, its role in ozone (O3)-induced acute lung injury (ALI) has never been tested. Here, we hypothesized that the loss of TTP would exacerbate O3-induced ALI and that the systemic overexpression of TTP would mitigate O3-induced ALI. Accordingly, TTP-knockout (TTPKO), airway epithelial cell-specific TTP-deficient (EpiKO), myeloid cell-specific TTP-deficient (MyeKO), and systemic TTP-overexpressing (TTPΔARE) adult male and female mice, along with their respective littermate control TTP-sufficient mice, were exposed to either O3 (3 ppm) or filtered air for 3 h. The endpoints, including bronchoalveolar lavage fluid cellularity, cytokine levels, and histopathological changes, were assessed 21 to 24 h after O3 or filtered air exposure. As compared with the O3-exposed TTP-sufficient mice, the O3-exposed TTPKO and O3-exposed cell-specific TTP-deficient mice exhibited a significant worsening of ALI outcomes (i.e., neutrophil infiltration, cytokine/chemokine production, and lung pathology). The severity of these outcomes was comparatively milder in O3-exposed EpiKO and O3-exposed MyeKO mice than in O3-exposed TTPKO mice. Conversely, the O3-exposed TTPΔARE mice were protected against O3-induced ALI, as indicated by relatively reduced levels of inflammatory cytokines/chemokines, reduced neutrophil infiltration, and mitigated lung pathology. Collectively, our data suggest that TTP is a critical regulator of inflammation in O3-induced ALI. These findings indicate that enhancing TTP expression could be a potential therapeutic strategy for simultaneously targeting multiple inflammatory cytokines in O3-induced ALI and possibly other inflammatory diseases.","journal":"The Journal of Immunology","year":2025,"id":537506,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9603,"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":371120,"name":"Ishita Choudhary","orcid":"0000-0001-8242-3928","position":1,"is_corresponding":false},{"id":1423739,"name":"Dhruthi Singamsetty","orcid":null,"position":2,"is_corresponding":false},{"id":451667,"name":"Sonika Patial","orcid":"0000-0002-7373-0835","position":3,"is_corresponding":false},{"id":451666,"name":"Yogesh Saini","orcid":"0000-0002-8324-2122","position":4,"is_corresponding":false},{"id":451662,"name":"Richa Lamichhane","orcid":"0009-0003-0722-658X","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-19T02:52:12.997494Z","pmid":"41379025","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":[]}