{"doi":"10.1172/jci136574","title":"ER-to-Golgi transport and SEC23-dependent COPII vesicles regulate T cell alloimmunity","abstract":"T cell-mediated responses are dependent on their secretion of key effector molecules. However, the critical molecular determinants of the secretion of these proteins are largely undefined. Here, we demonstrate that T cell activation increases trafficking via the ER-to-Golgi pathway. To study the functional role of this pathway, we generated mice with a T cell-specific deletion in SEC23B, a core subunit of coat protein complex II (COPII). We found that SEC23B critically regulated the T cell secretome following activation. SEC23B-deficient T cells exhibited a proliferative defect and reduced effector functions in vitro, as well as in experimental models of allogeneic and xenogeneic hematopoietic cell transplantation in vivo. However, T cells derived from 3 patients with congenital dyserythropoietic anemia II (CDAII), which results from Sec23b mutation, did not exhibit a similar phenotype. Mechanistic studies demonstrated that unlike murine KO T cells, T cells from patients with CDAII harbor increased levels of the closely related paralog, SEC23A. In vivo rescue of murine KO by expression of Sec23a from the Sec23b genomic locus restored T cell functions. Together, our data demonstrate a critical role for the COPII pathway, with evidence for functional overlap in vivo between SEC23 paralogs in the regulation of T cell immunity in both mice and humans.","journal":"Journal of Clinical Investigation","year":2021,"id":178111,"datarank":0.7818605988624227,"base_score":2.995732273553991,"endowment":2.995732273553991,"self_citation_contribution":0.4493598410330987,"citation_network_contribution":0.332500757829324,"self_endowment_contribution":0.4493598410330987,"citer_contribution":0.332500757829324,"corpus_percentile":null,"corpus_rank":null,"citation_count":19,"citer_count":19,"citers_with_citation_signal":12,"citers_with_endowment":12,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9546,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT02964494"]},"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":499041,"name":"Rami Khoriaty","orcid":"0000-0003-2539-5953","position":1,"is_corresponding":false},{"id":385965,"name":"Lu Li","orcid":"0000-0002-5496-7837","position":2,"is_corresponding":false},{"id":723834,"name":"Madison McClune","orcid":null,"position":3,"is_corresponding":false},{"id":479397,"name":"Theodosia A. Kalfa","orcid":"0000-0002-0426-9686","position":4,"is_corresponding":false},{"id":574383,"name":"Julia Wu","orcid":null,"position":5,"is_corresponding":false},{"id":385968,"name":"Daniel Peltier","orcid":"0000-0001-6069-9894","position":6,"is_corresponding":false},{"id":385966,"name":"Hideaki Fujiwara","orcid":"0000-0002-9720-3546","position":7,"is_corresponding":false},{"id":723237,"name":"Yaping Sun","orcid":"0000-0003-0801-563X","position":8,"is_corresponding":false},{"id":386755,"name":"Katherine Oravecz-Wilson","orcid":null,"position":9,"is_corresponding":false},{"id":85781,"name":"Richard A. King","orcid":"0000-0003-0519-8776","position":10,"is_corresponding":false},{"id":345469,"name":"David Ginsburg","orcid":"0000-0002-6436-8942","position":11,"is_corresponding":false},{"id":385969,"name":"Pavan Reddy","orcid":"0000-0001-7264-8429","position":12,"is_corresponding":false},{"id":378333,"name":"Stephanie Kim","orcid":"0000-0002-3894-8214","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-18T23:47:36.112170Z","pmid":"33463537","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":[]}