{"doi":"10.1101/2020.08.05.238360","title":"IFN- <i>γ</i> and TNF- <i>α</i> drive a <i>CXCL10</i> + <i>CCL2</i> + macrophage phenotype expanded in severe COVID-19 and other diseases with tissue inflammation","abstract":"Abstract Immunosuppressive and anti-cytokine treatment may have a protective effect for patients with COVID-19. Understanding the immune cell states shared between COVID-19 and other inflammatory diseases with established therapies may help nominate immunomodulatory therapies. Using an integrative strategy, we built a reference by meta-analyzing &gt; 300,000 immune cells from COVID-19 and 5 inflammatory diseases including rheumatoid arthritis (RA), Crohn’s disease (CD), ulcerative colitis (UC), lupus, and interstitial lung disease. Our cross-disease analysis revealed that an FCN1 + inflammatory macrophage state is common to COVID-19 bronchoalveolar lavage samples, RA synovium, CD ileum, and UC colon. We also observed that a CXCL10 + CCL2 + inflammatory macrophage state is abundant in severe COVID-19, inflamed CD and RA, and expresses inflammatory genes such as GBP1, STAT1 , and IL1B . We found that the CXCL10 + CCL2 + macrophages are transcriptionally similar to blood-derived macrophages stimulated with TNF- α and IFN- γ ex vivo . Our findings suggest that IFN- γ , alongside TNF- α , might be a key driver of this abundant inflammatory macrophage phenotype in severe COVID-19 and other inflammatory diseases, which may be targeted by existing immunomodulatory therapies.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":119012,"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":31,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9557,"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":226240,"name":"Joseph Mears","orcid":"0000-0002-0259-4055","position":1,"is_corresponding":false},{"id":552678,"name":"Lorien Shakib","orcid":"0000-0003-2502-2049","position":2,"is_corresponding":false},{"id":552679,"name":"Jessica I. Beynor","orcid":"0000-0001-9430-0271","position":3,"is_corresponding":false},{"id":552680,"name":"Sara Shanaj","orcid":"0000-0002-8945-7626","position":4,"is_corresponding":false},{"id":76148,"name":"Ilya Korsunsky","orcid":"0000-0003-4848-3948","position":5,"is_corresponding":false},{"id":291784,"name":"Aparna Nathan","orcid":"0000-0002-5975-2851","position":6,"is_corresponding":false},{"id":226219,"name":"Laura T. Donlin","orcid":"0000-0002-1428-090X","position":7,"is_corresponding":false},{"id":35259,"name":"Soumya Raychaudhuri","orcid":"0000-0002-1901-8265","position":8,"is_corresponding":false},{"id":226256,"name":"Fan Zhang","orcid":"0000-0002-6102-2970","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-18T23:14:03.409507Z","pmid":"32793902","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":[]}