title: Epigenetic Modification Mediates the Increase of LAG-3+T Cells in Chronic Osteomyelitis.
abstract: Immune suppression plays critical roles in the development of chronic osteomyelitis, and the mechanisms underlying the development of immune suppression in chronic osteomyelitis have attracted much attention. LAG-3 is an important suppressor of T cell activation, but the role of LAG-3 in the immune regulation of chronic osteomyelitis is currently unknown. We sought to demonstrate if LAG-3 plays crucial roles in chronic osteomyelitis progression and has effects on immune suppression and exhausting of T cells, and what is the mechanism underlying LAG-3 deregulation in chronic osteomyelitis. We examined the expression of LAG-3 in the T cells of peripheral blood of 50 healthy controls and 50 patients with chronic osteomyelitis by flow cytometry. Clinical data were analyzed to determine the correlation between inflammation index and LAG-3 expression. Moreover, we isolated the CD4+T cells from healthy controls and chronic osteomyelitis patients to compare cell proliferation and IFN-γ production. Chromatin immunoprecipitation assays were utilized to analyze the epigenetic modification on LAG-3 expression in T cells. We found that LAG-3 was significantly increased in the T cells of peripheral blood from chronic osteomyelitis patients. Subsequently, clinical data analysis suggested that the higher expression of LAG-3 was associated with severer inflammation situation. Consistently, LAG-3+CD4+T cells exhibited impaired cell proliferation and IFN-γ secretion. Deregulation of histone methylation mediated the increase of LAG-3+T cells during chronic osteomyelitis. Taken together, our study demonstrates the increase of LAG-3+T cells and its immune regulatory roles in chronic osteomyelitis progression, suggesting new mechanisms and potential therapeutic targets for chronic osteomyelitis.
authors.affiliation: Orthopaedic Department of Jinling Hospital, 305# East Zhongshan Road, Nanjing, Jiangsu Province, China.
authors.forename: Yicun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Orthopaedic Department of Jinling Hospital, 305# East Zhongshan Road, Nanjing, Jiangsu Province, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Orthopaedic Department of Jinling Hospital, 305# East Zhongshan Road, Nanjing, Jiangsu Province, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Meng
authors.affiliation: Orthopaedic Department of Jinling Hospital, 305# East Zhongshan Road, Nanjing, Jiangsu Province, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Orthopaedic Department of Jinling Hospital, 305# East Zhongshan Road, Nanjing, Jiangsu Province, China.
authors.forename: Jianning
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Orthopaedic Department of Jinling Hospital, 305# East Zhongshan Road, Nanjing, Jiangsu Province, China. qianhongbo1976@163.com.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Qian
authors.affiliation: Cardiology Department of Chinese PLA General Hospital, 28# Fuxing Road, Haidian District, Beijing, China. ilion31@163.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D049109:Cell Proliferation; D002908:Chronic Disease; D044127:Epigenesis, Genetic / Q000502:physiology*; D006801:Humans; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000276:immunology; D008213:Lymphocyte Activation; D010019:Osteomyelitis / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D000093322:Lymphocyte Activation Gene 3 Protein
chemical_list: D015703:Antigens, CD; D007371:Interferon-gamma; D000093322:Lymphocyte Activation Gene 3 Protein; C000720326:Lag3 protein, human
keywords: LAG-3; T cells; chronic osteomyelitis; epigenetic modification