title: Anti-Citrullinated Protein Antibodies Induce Macrophage Subset Disequilibrium in RA Patients.
abstract: We used samples from rheumatoid arthritis (RA) patients to examine whether Anti-citrullinated protein antibodies (ACPAs) alter macrophage subset distribution and promote RA development. Macrophage subset distributions and interferon regulatory factor 4 (IRF4) and IRF5 expressions were analyzed. ACPAs were purified by affinity column. After RA and osteoarthritis (OA) patients' macrophages were cocultured with ACPAs, macrophage subsets and IRF4 and IRF5 expressions were measured. Small interfering RNAs (siRNAs) were transfected into ACPA-activated cells to suppress IRF4 or IRF5. Fluorescence-activated cell sorting (FACS), Western blot, and immunohistochemistry were performed. Macrophage subset disequilibrium occurred in RA patient synovial fluids. IRF4 and IRF5 were all expressed in the synovial fluid and synovium. ACPAs (40 IU/ml) could induce macrophages to polarize to M1 subsets, and the percentage of increased M1/M2 ratio of RA patients was higher than that of the OA patients. ACPAs also induce IRF4 and IRF5 protein expressions. IRF5 siRNA transfection impaired ACPA activity significantly. We demonstrated that macrophage subset disequilibrium occurred in RA patients. ACPAs induced IRF5 activity and led to M1 macrophage polarization.
authors.affiliation: Department of Neurobiology, Neurobiology Key Laboratory, Harbin Medical University, Education Department of Heilongjiang Province, Harbin, Heilongjiang, 150081, China.|Department of Immunology, Mudanjiang Medical College, Mudanjiang, Heilongjiang, 157011, China.|The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Harbin, Heilongjiang Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Rheumatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150086, China.
authors.forename: Xiu
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150086, China.|The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Harbin, Heilongjiang Province, China.
authors.forename: Shaohong
authors.initials: S
authors.lastname: Fang
authors.affiliation: Department of Immunology, Mudanjiang Medical College, Mudanjiang, Heilongjiang, 157011, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Rheumatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150086, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurobiology, Neurobiology Key Laboratory, Harbin Medical University, Education Department of Heilongjiang Province, Harbin, Heilongjiang, 150081, China.
authors.forename: Tongshuai
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Neurobiology, Neurobiology Key Laboratory, Harbin Medical University, Education Department of Heilongjiang Province, Harbin, Heilongjiang, 150081, China.
authors.forename: Zhaoying
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Neurobiology, Neurobiology Key Laboratory, Harbin Medical University, Education Department of Heilongjiang Province, Harbin, Heilongjiang, 150081, China.
authors.forename: Yanwen
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Neurobiology, Neurobiology Key Laboratory, Harbin Medical University, Education Department of Heilongjiang Province, Harbin, Heilongjiang, 150081, China.
authors.forename: Siying
authors.initials: S
authors.lastname: Qu
authors.affiliation: Department of Neurobiology, Neurobiology Key Laboratory, Harbin Medical University, Education Department of Heilongjiang Province, Harbin, Heilongjiang, 150081, China.
authors.forename: Chuanliang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Laboratory Medicine, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China, 150086.
authors.forename: Fei
authors.initials: F
authors.lastname: Gao
authors.affiliation: Department of Sports Medicine, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China, 150086.
authors.forename: Haile
authors.initials: H
authors.lastname: Pan
authors.affiliation: Department of Neurobiology, Neurobiology Key Laboratory, Harbin Medical University, Education Department of Heilongjiang Province, Harbin, Heilongjiang, 150081, China.
authors.forename: Guangyou
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Neurobiology, Neurobiology Key Laboratory, Harbin Medical University, Education Department of Heilongjiang Province, Harbin, Heilongjiang, 150081, China. lihulun@aliyun.com.|The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Harbin, Heilongjiang Province, China. lihulun@aliyun.com.
authors.forename: Hulun
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Neurobiology, Neurobiology Key Laboratory, Harbin Medical University, Education Department of Heilongjiang Province, Harbin, Heilongjiang, 150081, China. sunbo720@aliyun.com.|The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Harbin, Heilongjiang Province, China. sunbo720@aliyun.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Sun
mesh_terms: D001172:Arthritis, Rheumatoid / Q000097:blood / Q000235:genetics / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D016022:Case-Control Studies; D002478:Cells, Cultured; D002956:Citrulline / Q000276:immunology*; D005260:Female; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008297:Male; D010455:Peptides / Q000276:immunology*; D010641:Phenotype; D034622:RNA Interference; D013582:Synovial Fluid / Q000276:immunology / Q000378:metabolism; D014162:Transfection; D000099218:Interferon Regulatory Factor-4
chemical_list: D001323:Autoantibodies; D002956:Citrulline; D050835:Interferon Regulatory Factors; D010455:Peptides; D000099218:Interferon Regulatory Factor-4; C431713:IRF5 protein, human
keywords: ACPAs; IRF5; macrophage subset; rheumatoid arthritis