{"doi":"10.1111/ajt.16861","title":"Genetically targeting the BATF family transcription factors BATF and BATF3 in the mouse abrogates effector T cell activities and enables long-term heart allograft survival","abstract":"T cells must be activated and become effectors first before executing allograft rejection, a process that is regulated by diverse signals and transcription factors. In this study, we studied the basic leucine zipper ATF-like transcription factor (BATF) family members in regulating T cell activities in a heart transplant model and found that mice deficient for both BATF and BATF3 (Batf−/−Batf3−/− mice) spontaneously accept the heart allografts long-term without tolerizing therapies. Similarly, adoptive transfer of wild type T cells into Rag1−/− hosts induced prompt rejection of heart and skin allografts, whereas the Batf−/−Batf3−/− T cells failed to do so. Analyses of graft-infiltrating cells showed that Batf−/−Batf3−/− T cells infiltrate the graft but fail to acquire an effector phenotype (CD44highKLRG1+). Co-transfer experiments in a T cell receptor transgenic TEa model revealed that the Batf−/−Batf3−/− T cells fail to expand in vivo, retain a quiescent phenotype (CD62L+CD127+), and unable to produce effector cytokines to alloantigen stimulation, which contrasted sharply to that of wild type T cells. Together, our data demonstrate that the BATF and BATF3 are critical regulators of T effector functions, thus making them attractive targets for therapeutic interventions in transplant settings. T cells must be activated and become effectors first before executing allograft rejection, a process that is regulated by diverse signals and transcription factors. In this study, we studied the basic leucine zipper ATF-like transcription factor (BATF) family members in regulating T cell activities in a heart transplant model and found that mice deficient for both BATF and BATF3 (Batf−/−Batf3−/− mice) spontaneously accept the heart allografts long-term without tolerizing therapies. Similarly, adoptive transfer of wild type T cells into Rag1−/− hosts induced prompt rejection of heart and skin allografts, whereas the Batf−/−Batf3−/− T cells failed to do so. Analyses of graft-infiltrating cells showed that Batf−/−Batf3−/− T cells infiltrate the graft but fail to acquire an effector phenotype (CD44highKLRG1+). Co-transfer experiments in a T cell receptor transgenic TEa model revealed that the Batf−/−Batf3−/− T cells fail to expand in vivo, retain a quiescent phenotype (CD62L+CD127+), and unable to produce effector cytokines to alloantigen stimulation, which contrasted sharply to that of wild type T cells. Together, our data demonstrate that the BATF and BATF3 are critical regulators of T effector functions, thus making them attractive targets for therapeutic interventions in transplant settings.","journal":"American Journal of Transplantation","year":2021,"id":176774,"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":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9561,"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":329073,"name":"Xiang Xiao","orcid":"0000-0001-6644-6118","position":1,"is_corresponding":false},{"id":719600,"name":"Gangcheng Kong","orcid":"0000-0002-1581-8257","position":2,"is_corresponding":false},{"id":720152,"name":"Mou Wen","orcid":null,"position":3,"is_corresponding":false},{"id":509929,"name":"Guangchuan Wang","orcid":"0000-0002-5113-3773","position":4,"is_corresponding":false},{"id":720153,"name":"Rafik M. 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