{"doi":"10.3389/fimmu.2021.618807","title":"Cyclic-di-GMP Induces STING-Dependent ILC2 to ILC1 Shift During Innate Type 2 Lung Inflammation","abstract":"Type 2 inflammation is found in most forms of asthma, which may co-exist with recurrent viral infections, bacterial colonization, and host cell death. These processes drive the accumulation of intracellular cyclic-di-nucleotides such as cyclic-di-GMP (CDG). Group 2 innate lymphoid cells (ILC2s) are critical drivers of type 2 lung inflammation during fungal allergen exposure in mice; however, it is unclear how CDG regulates lung ILC responses during lung inflammation. Here, we show that intranasal CDG induced early airway type 1 interferon (IFN) production and dramatically suppressed CD127+ST2+ ILC2s and type 2 lung inflammation during Alternaria and IL-33 exposure. Further, CD127–ST2–Thy1.2+ lung ILCs, which showed a transcriptomic signature consistent with ILC1s, were expanded and activated by CDG combined with either Alternaria or IL-33. CDG-mediated suppression of type 2 inflammation occurred independent of IL-18R, IL-12, and STAT6 but required the stimulator of interferon genes (STING) and type 1 IFN signaling. Thus, CDG potently suppresses ILC2-driven lung inflammation and promotes ILC1 responses. These results suggest potential therapeutic modulation of STING to suppress type 2 inflammation and/or increase anti-viral responses during respiratory infections.","journal":"Frontiers in Immunology","year":2021,"id":186198,"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":24,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9504,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":743512,"name":"Jana Badrani","orcid":"0000-0001-6479-7969","position":1,"is_corresponding":false},{"id":744193,"name":"Luay H. Naji","orcid":null,"position":2,"is_corresponding":false},{"id":744194,"name":"Michael Amadeo","orcid":null,"position":3,"is_corresponding":false},{"id":744195,"name":"Anthea Leng","orcid":null,"position":4,"is_corresponding":false},{"id":743513,"name":"Lee Lacasa","orcid":"0000-0002-2240-8715","position":5,"is_corresponding":false},{"id":743514,"name":"Allyssa Strohm","orcid":"0000-0003-1025-5333","position":6,"is_corresponding":false},{"id":744196,"name":"Samantha Renusch","orcid":null,"position":7,"is_corresponding":false},{"id":744197,"name":"Suzanna Gasparian","orcid":null,"position":8,"is_corresponding":false},{"id":385678,"name":"Taylor A. Doherty","orcid":"0000-0003-3256-0398","position":9,"is_corresponding":false},{"id":385677,"name":"Kellen Cavagnero","orcid":"0000-0003-4160-6394","position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":null,"created_at":"2026-07-18T23:48:42.632147Z","pmid":"33679760","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":[]}