{"doi":"10.1007/s11481-020-09909-8","title":"Crohn’s and Parkinson’s Disease-Associated LRRK2 Mutations Alter Type II Interferon Responses in Human CD14+ Blood Monocytes Ex Vivo","abstract":"Abstract The Leucine Rich Repeat Kinase 2 ( LRRK2 ) is one of causative genes of familial Parkinson’s disease (PD). The M2397T polymorphism in LRRK2 is genetically associated with sporadic Crohn’s disease (CD). LRRK2 is expressed in human CD14 + monocytes, induced by interferon-γ (IFN-γ) and suppresses inflammatory activation. We hypothesize that IFN-γ-induced LRRK2 and inflammatory gene expression is altered by LRRK2 genetic polymorphism found in CD and PD cases. A total of 46 CD and 51 control cases, and 16 PD cases and 16 PD-linked LRRK2 mutation cases were recruited. Live human CD14 + monocytes were isolated from donors for ex vivo IFN-γ stimulation and gene expression analysis. IFN-γ potently enhanced TNFA, IL12, HLADRA1 and LRRK2 expression, which was suppressed by FK506, a calcineurin-specific inhibitor, but further enhanced by LRRK2-specific kinase inhibitor (GSK2578215A). The 2397-M/M CD risk allele enhanced IFN-γ responses of CD14 + cells in CD but not in control group. CD14 + monocytes from G2019S and R1441C LRRK2 mutated PD cases and carriers show no changes in IFN-γ responses for TNFA or IL12 , reduced response for HLADRA1, and enhanced responses for LRRK2 in FK506-sensitive manner. These data demonstrate that CD-associated LRRK2 mutations are significant modifiers of innate immune response in CD14 + monocytes, and PD-associated LRRK2 mutation may contribute to reduced antigen presentation response.","journal":"Journal of Neuroimmune Pharmacology","year":2020,"id":103813,"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":24,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9588,"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":483803,"name":"Lacin Koro","orcid":null,"position":1,"is_corresponding":false},{"id":266497,"name":"Benjamin Wolozin","orcid":"0000-0003-2068-1475","position":2,"is_corresponding":false},{"id":16019,"name":"Francis A. Farraye","orcid":"0000-0001-6371-2441","position":3,"is_corresponding":false},{"id":505040,"name":"Audrey Strongosky","orcid":"0000-0003-4734-0339","position":4,"is_corresponding":false},{"id":17548,"name":"Zbigniew K. Wszołek","orcid":"0000-0001-5487-1053","position":5,"is_corresponding":false},{"id":236493,"name":"Tsuneya Ikezu","orcid":"0000-0002-3979-8596","position":0,"is_corresponding":true}],"reference_count":20,"raw_metadata":null,"created_at":"2026-07-18T22:42:48.999009Z","pmid":"32180132","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":[]}