{"doi":"10.3389/fimmu.2024.1360229","title":"Homeodomain-only protein suppresses proliferation and contributes to differentiation- and age-related reduced CD8+ T cell expansion","abstract":"T cell activation is a tightly controlled process involving both positive and negative regulators. The precise mechanisms governing the negative regulators in T cell proliferation remain incompletely understood. Here, we report that homeodomain-only protein (HOPX), a homeodomain-containing protein, and its most abundant isoform HOPXb , negatively regulate activation-induced proliferation of human T cells. We found that HOPX expression progressively increased from naïve (T N ) to central memory (T CM ) to effector memory (T EM ) cells, with a notable upregulation following in vitro stimulation. Overexpression of HOPXb leads to a reduction in T N cell proliferation while HOPX knockdown promotes proliferation of T N and T EM cells. Furthermore, we demonstrated that HOPX binds to promoters and exerts repressive effects on the expression of MYC and NR4A1 , two positive regulators known to promote T cell proliferation. Importantly, our findings suggest aging is associated with increased HOPX expression, and that knockdown of HOPX enhances the proliferation of CD8 + T cells in older adults. Our findings provide compelling evidence that HOPX serves as a negative regulator of T cell activation and plays a pivotal role in T cell differentiation and in age-related-reduction in T cell proliferation.","journal":"Frontiers in Immunology","year":2024,"id":479455,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9466,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1318941,"name":"Michael S. Patrick","orcid":null,"position":1,"is_corresponding":false},{"id":302661,"name":"Jian Lü","orcid":"0000-0002-4409-1667","position":2,"is_corresponding":false},{"id":799814,"name":"Joseph Chen","orcid":"0000-0002-2325-4498","position":3,"is_corresponding":false},{"id":63921,"name":"Yongqing Zhang","orcid":"0000-0003-3422-8305","position":4,"is_corresponding":false},{"id":860993,"name":"Humza Hemani","orcid":"0000-0003-1766-683X","position":5,"is_corresponding":false},{"id":451858,"name":"Elin Lehrmann","orcid":"0000-0002-9869-9475","position":6,"is_corresponding":false},{"id":275722,"name":"Supriyo De","orcid":"0000-0002-2075-7655","position":7,"is_corresponding":false},{"id":420559,"name":"Nan‐ping Weng","orcid":"0000-0001-8175-8953","position":8,"is_corresponding":false},{"id":1114363,"name":"Qian Yang","orcid":"0000-0002-4777-2548","position":0,"is_corresponding":true}],"reference_count":32,"raw_metadata":null,"created_at":"2026-07-19T02:06:54.284166Z","pmid":"38410516","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":[]}