{"doi":"10.1101/2021.08.05.455061","title":"Th1/17 Cells Infiltrate Murine Cytomegalovirus-Infected Renal Allografts via Virus-Induced CCL20 and Promote Th1 Cells through IL-17A","abstract":"ABSTRACT Cytomegalovirus (CMV) infection is associated with renal allograft failure by unknown mechanisms. In a murine renal transplant model, murine CMV (MCMV) induces intragraft infiltration of Th17 cells co-expressing Th1 cytokines, IFN-γ and TNF-α, but only a minority of intragraft Th17 cells are specific for MCMV antigens. Instead, MCMV promotes viral antigen-independent Th17 cell recruitment via CCL20-CCR6 and CXCL10-CXCR3 interactions. Th17 cells correlate directly with Th1 cell frequencies and inversely with Tregs in MCMV infected grafts. Pharmacologic inhibition of IL-17A reduces intragraft Th17 cells and neutrophils, increases Tregs, and reduces total but not MCMV-specific Th1 cells. Among a clinical renal transplant cohort with acute rejection, patients with CMV DNAemia had significantly higher serum IL-17A quantities compared to those without CMV DNAemia. Together, these findings indicate that CMV infection upregulates Th17 cell activity during acute rejection and suggests that inhibition of IL-17A may ameliorate CMV-associated allograft injury without impairing antiviral Th1 cells.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":219197,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9536,"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":817359,"name":"Shashi Anand","orcid":"0000-0002-7226-7113","position":1,"is_corresponding":false},{"id":817360,"name":"Qiang Zeng","orcid":"0000-0003-2372-3466","position":2,"is_corresponding":false},{"id":300253,"name":"Victoria M. Velazquez","orcid":null,"position":3,"is_corresponding":false},{"id":817361,"name":"Srinivasa R. Boddeda","orcid":"0000-0003-3646-028X","position":4,"is_corresponding":false},{"id":692500,"name":"James Fitch","orcid":"0000-0001-8009-899X","position":5,"is_corresponding":false},{"id":303249,"name":"Ranjana W. Minz","orcid":null,"position":6,"is_corresponding":false},{"id":817362,"name":"Mukut Minz","orcid":"0000-0002-0824-5462","position":7,"is_corresponding":false},{"id":817363,"name":"Ashish Sharma","orcid":"0000-0003-3349-4417","position":8,"is_corresponding":false},{"id":579636,"name":"Rachel E. Cianciolo","orcid":"0000-0001-8213-9361","position":9,"is_corresponding":false},{"id":651170,"name":"Masako Shimamura","orcid":"0009-0008-9952-351X","position":10,"is_corresponding":false},{"id":817358,"name":"Ravi Dhital","orcid":"0000-0001-6180-2128","position":0,"is_corresponding":true}],"reference_count":93,"raw_metadata":null,"created_at":"2026-07-18T23:53:33.915158Z","pmid":null,"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":[]}