{"doi":"10.3389/fimmu.2021.641188","title":"A Requirement of Protein Geranylgeranylation for Chemokine Receptor Signaling and Th17 Cell Function in an Animal Model of Multiple Sclerosis","abstract":"Precisely controlled lymphocyte migration is critically required for immune surveillance and successful immune responses. Lymphocyte migration is strictly regulated by chemokines and chemokine receptors. Here we show that protein geranylgeranylation, a form of post-translational protein lipid modification, is required for chemokine receptor-proximal signaling. Mature thymocytes deficient for protein geranylgeranylation are impaired for thymus egress. Circulating mature T cells lacking protein geranylgeranylation fail to home to secondary lymphoid organs or to transmigrate in response to chemokines in vitro . Mechanistically, protein geranylgeranylation modifies the γ-subunits of the heterotrimeric small GTPases that are essential for chemokine receptor signaling. In addition, protein geranylgeranylation also promotes the differentiation of IL-17-producing T helper cells while inhibiting the differentiation of Foxp3 + regulatory T cells. Finally, mice with T cell lineage-specific deficiency of protein geranylgeranylation are resistant to experimental autoimmune encephalomyelitis induction. This study elucidated a critical role of protein geranylgeranylation in regulating T lymphocyte migration and function.","journal":"Frontiers in Immunology","year":2021,"id":202236,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.954,"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":781806,"name":"Jia Geng","orcid":"0000-0003-2638-3479","position":1,"is_corresponding":false},{"id":781807,"name":"Eunchong Park","orcid":"0000-0001-8018-664X","position":2,"is_corresponding":false},{"id":261428,"name":"Quanquan Ding","orcid":null,"position":3,"is_corresponding":false},{"id":554300,"name":"John Zhou","orcid":"0000-0003-3565-5376","position":4,"is_corresponding":false},{"id":782272,"name":"Ciana Walcott","orcid":null,"position":5,"is_corresponding":false},{"id":782273,"name":"Junyi J. Zhang","orcid":null,"position":6,"is_corresponding":false},{"id":366373,"name":"Hsin-I Huang","orcid":"0000-0001-9106-9449","position":7,"is_corresponding":false},{"id":366378,"name":"Gianna Hammer","orcid":"0000-0001-6959-858X","position":8,"is_corresponding":false},{"id":781808,"name":"Donghai Wang","orcid":"0000-0003-4273-6115","position":9,"is_corresponding":false},{"id":781805,"name":"Gregory Swan","orcid":"0000-0002-8038-3851","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-18T23:51:05.955461Z","pmid":"33828552","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":[]}