{"doi":"10.1101/2020.12.04.412056","title":"Granzyme B prevents aberrant IL-17 production and intestinal pathogenicity in CD4 <sup>+</sup> T cells","abstract":"Abstract CD4 + T cell activation and differentiation are important events that set the stage for proper immune responses. Many factors are involved in the activation and differentiation of T cells, and these events are tightly controlled to prevent unwanted and/or exacerbated immune responses that may harm the host. It has been well documented that granzyme B, a potent serine protease involved in cell-mediated cytotoxicity, is readily expressed by certain CD4 + T cells, such as regulatory T cells and CD4 + CD8αα + intestinal intraepithelial lymphocytes, both of which display cytotoxicity associated with granzyme B. However, because not all CD4 + T cells expressing granzyme B are cytotoxic, additional roles for this protease in CD4 + T cell biology remain unknown. Here, using a combination of in vivo and in vitro approaches, we report that granzyme B-deficient CD4 + T cells display increased IL-17 production. In the adoptive transfer model of intestinal inflammation, granzyme B-deficient CD4 + T cells triggered a more rapid disease onset than their WT counterparts, and presented a differential transcription profile. Similar results were also observed in granzyme B-deficient mice infected with Citrobacter rodentium . Our results suggest that granzyme B modulates CD4 + T cell differentiation, providing a new perspective into the biology of this enzyme.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":132336,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9552,"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":588452,"name":"Michael J. Greer","orcid":null,"position":1,"is_corresponding":false},{"id":588008,"name":"Kathleen G. McClanahan","orcid":"0000-0002-0582-3634","position":2,"is_corresponding":false},{"id":588009,"name":"Ali Nazmi","orcid":"0000-0001-9258-1575","position":3,"is_corresponding":false},{"id":263090,"name":"M. Blanca Piazuelo","orcid":"0000-0002-0000-1324","position":4,"is_corresponding":false},{"id":480180,"name":"Kshipra Singh","orcid":null,"position":5,"is_corresponding":false},{"id":60566,"name":"Keith T. Wilson","orcid":"0000-0003-4421-1830","position":6,"is_corresponding":false},{"id":588010,"name":"Danyvid Olivares–Villagómez","orcid":"0000-0002-1158-8976","position":7,"is_corresponding":false},{"id":588451,"name":"Kristen L. Hoek","orcid":null,"position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-18T23:16:10.654971Z","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":[]}