Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
General Research Article

Identifying the Hub Genes and Immune Cell Infiltration in Synovial Tissue between Osteoarthritic and Rheumatoid Arthritic Patients by Bioinformatic Approach

Author(s): Junjie Wang, Qin Fan, Tengbo Yu* and Yingze Zhang*

Volume 28, Issue 6, 2022

Published on: 04 November, 2021

Page: [497 - 509] Pages: 13

DOI: 10.2174/1381612827666211104154459

Price: $65

Open Access Journals Promotions 2
conference banner
Abstract

Background: Osteoarthritis (OA) and rheumatoid arthritis (RA) are two common diseases that result in limb disability and a decrease in quality of life. The major symptoms of OA and RA are pain, swelling, stiffness, and malformation of joints, and each disease also has unique characteristics.

Objective: To compare the pathological mechanisms of OA and RA via weighted correlation network analysis (WGCNA) and immune infiltration analysis and find potential diagnostic and pharmaceutical targets for the treatment of OA and RA.

Methods: The gene expression profiles of ten OA and ten RA synovial tissue samples were downloaded from the Gene Expression Omnibus (GEO) database (GSE55235). After obtaining differentially expressed genes (DEGs) via GEO2R, WGCNA was conducted using an R package, and modules and genes that were highly correlated with OA and RA were identified. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and protein-protein interaction (PPI) network analyses were also conducted. Hub genes were identified using the Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape software. Immune infiltration analysis was conducted using the Perl program and CIBERSORT software.

Results: Two hundred ninety-nine DEGs, 24 modules, 16 GO enrichment terms, 6 KEGG pathway enrichment terms, 10 hub genes (CXCL9, CXCL10, CXCR4, CD27, CD69, CD3D, IL7R, STAT1, RGS1, and ISG20), and 8 kinds of different infiltrating immune cells (plasma cells, CD8 T cells, activated memory CD4 T cells, T helper follicular cells, M1 macrophages, Tregs, resting mast cells, and neutrophils) were found to be involved in the different pathological mechanisms of OA and RA.

Conclusion: Inflammation-associated genes were the top differentially expressed hub genes between OA and RA, and their expression was downregulated in OA. Genes associated with lipid metabolism may have upregulated expression in OA. In addition, immune cells that participate in the adaptive immune response play an important role in RA. OA mainly involves immune cells that are associated with the innate immune response.

Keywords: Osteoarthritis, rheumatoid arthritis, GEO, WGCNA, immune infiltration, bioinformation.

« Previous
[1]
Prieto-Alhambra D, Judge A, Javaid MK, Cooper C, Diez-Perez A, Arden NK. Incidence and risk factors for clinically diagnosed knee, hip and hand osteoarthritis: Influences of age, gender and osteoarthritis affecting other joints. Ann Rheum Dis 2014; 73(9): 1659-64.
[http://dx.doi.org/10.1136/annrheumdis-2013-203355] [PMID: 23744977]
[2]
Jones ME, Davies MAM, Shah K, et al. The prevalence of hand and wrist osteoarthritis in elite former cricket and rugby union players. J Sci Med Sport 2019; 22(8): 871-5.
[http://dx.doi.org/10.1016/j.jsams.2019.03.004] [PMID: 30940442]
[3]
Heijink A, Vanhees M, van den Ende K, et al. Biomechanical considerations in the pathogenesis of osteoarthritis of the elbow. Knee Surg Sports Traumatol Arthrosc 2016; 24(7): 2313-8.
[http://dx.doi.org/10.1007/s00167-015-3518-7] [PMID: 25677500]
[4]
Ryd L, Brittberg M, Eriksson K, et al. Pre-osteoarthritis: Definition and diagnosis of an elusive clinical entity. Cartilage 2015; 6(3): 156-65.
[http://dx.doi.org/10.1177/1947603515586048] [PMID: 26175861]
[5]
Turkiewicz A, Petersson IF, Björk J, et al. Current and future impact of osteoarthritis on health care: A population-based study with projections to year 2032. Osteoarthritis Cartilage 2014; 22(11): 1826-32.
[http://dx.doi.org/10.1016/j.joca.2014.07.015] [PMID: 25084132]
[6]
Li MH, Xiao R, Li JB, Zhu Q. Regenerative approaches for cartilage repair in the treatment of osteoarthritis. Osteoarthritis Cartilage 2017; 25(10): 1577-87.
[http://dx.doi.org/10.1016/j.joca.2017.07.004] [PMID: 28705606]
[7]
Goldring MB, Otero M. Inflammation in osteoarthritis. Curr Opin Rheumatol 2011; 23(5): 471-8.
[http://dx.doi.org/10.1097/BOR.0b013e328349c2b1] [PMID: 21788902]
[8]
Brandt KD, Radin EL, Dieppe PA, van de Putte L. Yet more evidence that osteoarthritis is not a cartilage disease. Ann Rheum Dis 2006; 65(10): 1261-4.
[http://dx.doi.org/10.1136/ard.2006.058347] [PMID: 16973787]
[9]
Silverwood V, Blagojevic-Bucknall M, Jinks C, Jordan JL, Protheroe J, Jordan KP. Current evidence on risk factors for knee osteoarthritis in older adults: A systematic review and meta-analysis. Osteoarthritis Cartilage 2015; 23(4): 507-15.
[http://dx.doi.org/10.1016/j.joca.2014.11.019] [PMID: 25447976]
[10]
Bijlsma JW, Berenbaum F, Lafeber FP. Osteoarthritis: An update with relevance for clinical practice. Lancet 2011; 377(9783): 2115-26.
[http://dx.doi.org/10.1016/S0140-6736(11)60243-2] [PMID: 21684382]
[11]
Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. Lancet 2016; 388(10055): 2023-38.
[http://dx.doi.org/10.1016/S0140-6736(16)30173-8] [PMID: 27156434]
[12]
Smolen JS, Aletaha D, Barton A, et al. Rheumatoid arthritis. Nat Rev Dis Primers 2018; 4: 18001.
[http://dx.doi.org/10.1038/nrdp.2018.1] [PMID: 29417936]
[13]
Parks CG, Walitt BT, Pettinger M, et al. Insecticide use and risk of rheumatoid arthritis and systemic lupus erythematosus in the Women’s Health Initiative Observational Study. Arthritis Care Res (Hoboken) 2011; 63(2): 184-94.
[http://dx.doi.org/10.1002/acr.20335] [PMID: 20740609]
[14]
Kobayashi S, Okamoto H, Iwamoto T, et al. A role for the aryl hydrocarbon receptor and the dioxin TCDD in rheumatoid arthritis. Rheumatology 2008; 47(9): 1317-22.
[http://dx.doi.org/10.1093/rheumatology/ken259] [PMID: 18617548]
[15]
Taylor PC, Keystone EC, van der Heijde D, et al. Baricitinib versus placebo or adalimumab in rheumatoid arthritis. N Engl J Med 2017; 376(7): 652-62.
[http://dx.doi.org/10.1056/NEJMoa1608345] [PMID: 28199814]
[16]
Ungethuem U, Haeupl T, Witt H, et al. Molecular signatures and new candidates to target the pathogenesis of rheumatoid arthritis. Physiol Genomics 2010; 42A(4): 267-82.
[http://dx.doi.org/10.1152/physiolgenomics.00004.2010] [PMID: 20858714]
[17]
Firestein GS. Evolving concepts of rheumatoid arthritis. Nature 2003; 423(6937): 356-61.
[http://dx.doi.org/10.1038/nature01661] [PMID: 12748655]
[18]
Aihaiti Y, Tuerhong X, Ye JT, Ren XY, Xu P. Identification of pivotal genes and pathways in the synovial tissue of patients with rheumatoid arthritis and osteoarthritis through integrated bioinformatic analysis. Mol Med Rep 2020; 22(4): 3513-24.
[http://dx.doi.org/10.3892/mmr.2020.11406] [PMID: 32945465]
[19]
Zuo B, Zhu J, Xiao F, Wang C, Shen Y, Chen X. Identification of novel biomarkers and candidate small molecule drugs in rheumatoid arthritis and osteoarthritis based on bioinformatics analysis of high-throughput data. Biosci Rep 2020; 40(12)BSR20193823
[http://dx.doi.org/10.1042/BSR20193823] [PMID: 33325525]
[20]
Meng Q, Qiu B. Exosomal microRNA-320a derived from mesenchymal stem cells regulates rheumatoid arthritis fibroblast-like synoviocyte activation by suppressing CXCL9 expression. Front Physiol 2020; 11: 441.
[http://dx.doi.org/10.3389/fphys.2020.00441] [PMID: 32528301]
[21]
Yoshida S, Arakawa F, Higuchi F, et al. Gene expression analysis of rheumatoid arthritis synovial lining regions by cDNA microarray combined with laser microdissection: Up-regulation of inflammation-associated STAT1, IRF1, CXCL9, CXCL10, and CCL5. Scand J Rheumatol 2012; 41(3): 170-9.
[http://dx.doi.org/10.3109/03009742.2011.623137] [PMID: 22401175]
[22]
Bustamante MF, Garcia-Carbonell R, Whisenant KD, Guma M. Fibroblast-like synoviocyte metabolism in the pathogenesis of rheumatoid arthritis. Arthritis Res Ther 2017; 19(1): 110.
[http://dx.doi.org/10.1186/s13075-017-1303-3]
[23]
Yarilina A, Park-Min KH, Antoniv T, Hu X, Ivashkiv LB. TNF activates an IRF1-dependent autocrine loop leading to sustained expression of chemokines and STAT1-dependent type I interferon-response genes. Nat Immunol 2008; 9(4): 378-87.
[http://dx.doi.org/10.1038/ni1576] [PMID: 18345002]
[24]
Yu F, Xie Y, Wang Y, Peng ZH, Li J, Oupický D. Chloroquine-containing HPMA copolymers as polymeric inhibitors of cancer cell migration mediated by the CXCR4/SDF-1 chemokine axis. ACS Macro Lett 2016; 5(3): 342-5.
[http://dx.doi.org/10.1021/acsmacrolett.5b00857] [PMID: 27795873]
[25]
Nanki T, Takada K, Komano Y, et al. Chemokine receptor expression and functional effects of chemokines on B cells: Implication in the pathogenesis of rheumatoid arthritis. Arthritis Res Ther 2009; 11(5): R149.
[http://dx.doi.org/10.1186/ar2823] [PMID: 19804625]
[26]
Dymock DC, Brown MP, Merritt KA, Trumble TN. Concentrations of stromal cell-derived factor-1 in serum, plasma, and synovial fluid of horses with osteochondral injury. Am J Vet Res 2014; 75(8): 722-30.
[http://dx.doi.org/10.2460/ajvr.75.8.722] [PMID: 25061703]
[27]
Kanbe K, Takemura T, Takeuchi K, Chen Q, Takagishi K, Inoue K. Synovectomy reduces stromal-cell-derived factor-1 (SDF-1) which is involved in the destruction of cartilage in osteoarthritis and rheumatoid arthritis. J Bone Joint Surg Br 2004; 86(2): 296-300.
[http://dx.doi.org/10.1302/0301-620X.86B2.14474] [PMID: 15046450]
[28]
Peng L, Zhu N, Mao J, et al. Expression levels of CXCR4 and CXCL12 in patients with rheumatoid arthritis and its correlation with disease activity. Exp Ther Med 2020; 20(3): 1925-34.
[PMID: 32782501]
[29]
Hartgring SA, van Roon JA, Wenting-van Wijk M, et al. Elevated expression of interleukin-7 receptor in inflamed joints mediates interleukin-7-induced immune activation in rheumatoid arthritis. Arthritis Rheum 2009; 60(9): 2595-605.
[http://dx.doi.org/10.1002/art.24754] [PMID: 19714586]
[30]
Hintzen RQ, van Lier RA, Kuijpers KC, et al. Elevated levels of a soluble form of the T cell activation antigen CD27 in cerebrospinal fluid of multiple sclerosis patients. J Neuroimmunol 1991; 35(1-3): 211-7.
[http://dx.doi.org/10.1016/0165-5728(91)90175-7] [PMID: 1659587]
[31]
Sun H, Zhang Y, Song W, et al. IgM+CD27+ B cells possessed regulatory function and represented the main source of B cell-derived IL-10 in the synovial fluid of osteoarthritis patients. Hum Immunol 2019; 80(4): 263-9.
[http://dx.doi.org/10.1016/j.humimm.2019.02.007] [PMID: 30769033]
[32]
Afeltra A, Galeazzi M, Ferri GM, et al. Expression of CD69 antigen on synovial fluid T cells in patients with rheumatoid arthritis and other chronic synovitis. Ann Rheum Dis 1993; 52(6): 457-60.
[http://dx.doi.org/10.1136/ard.52.6.457] [PMID: 8323399]
[33]
Fernández-Gutiérrez B, Hernández-García C, Bañares AA, Jover JA. Characterization and regulation of CD69 expression on rheumatoid arthritis synovial fluid T cells. J Rheumatol 1995; 22(3): 413-20.
[PMID: 7783055]
[34]
Tak PP, Hintzen RQ, Teunissen JJ, et al. Expression of the activation antigen CD27 in rheumatoid arthritis. Clin Immunol Immunopathol 1996; 80(2): 129-38.
[http://dx.doi.org/10.1006/clin.1996.0106] [PMID: 8764557]
[35]
Rollín R, Marco F, Jover JA, et al. Early lymphocyte activation in the synovial microenvironment in patients with osteoarthritis: Comparison with rheumatoid arthritis patients and healthy controls. Rheumatol Int 2008; 28(8): 757-64.
[http://dx.doi.org/10.1007/s00296-008-0518-7] [PMID: 18205004]
[36]
Mucke J, Hoyer A, Brinks R, et al. Inhomogeneity of immune cell composition in the synovial sublining: Linear mixed modelling indicates differences in distribution and spatial decline of CD68+ macrophages in osteoarthritis and rheumatoid arthritis. Arthritis Res Ther 2016; 18: 170.
[http://dx.doi.org/10.1186/s13075-016-1057-3] [PMID: 27424032]
[37]
de la Hera A, Müller U, Olsson C, Isaaz S, Tunnacliffe A. Structure of the T cell antigen receptor (TCR): Two CD3 epsilon subunits in a functional TCR/CD3 complex. J Exp Med 1991; 173(1): 7-17.
[http://dx.doi.org/10.1084/jem.173.1.7] [PMID: 1824636]
[38]
Lee JK, Bou Dagher J. Regulator of G-protein signaling (RGS)1 and RGS10 proteins as potential drug targets for neuroinflammatory and neurodegenerative diseases. AAPS J 2016; 18(3): 545-9.
[http://dx.doi.org/10.1208/s12248-016-9883-4] [PMID: 26902301]
[39]
Hu X, Tang J, Zeng G, Hu X, Bao P. RGS1 silencing inhibits the inflammatory response and angiogenesis in rheumatoid arthritis rats through the inactivation of Toll-like receptor signaling pathway. 2019; 234(11): 20432-42.
[40]
Espert L, Rey C, Gonzalez L, et al. The exonuclease ISG20 is directly induced by synthetic dsRNA via NF-kappaB and IRF1 activation. Oncogene 2004; 23(26): 4636-40.
[http://dx.doi.org/10.1038/sj.onc.1207586] [PMID: 15064705]
[41]
Chang X, Yue L, Liu W, et al. CD38 and E2F transcription factor 2 have uniquely increased expression in rheumatoid arthritis synovial tissues. Clin Exp Immunol 2014; 176(2): 222-31.
[http://dx.doi.org/10.1111/cei.12268] [PMID: 24397353]
[42]
Balandraud N, Meynard JB, Auger I, et al. Epstein-Barr virus load in the peripheral blood of patients with rheumatoid arthritis: Accurate quantification using real-time polymerase chain reaction. Arthritis Rheum 2003; 48(5): 1223-8.
[http://dx.doi.org/10.1002/art.10933] [PMID: 12746895]
[43]
Lünemann JD, Frey O, Eidner T, et al. Increased frequency of EBV-specific effector memory CD8+ T cells correlates with higher viral load in rheumatoid arthritis. J Immunol 2008; 181(2): 991-1000.
[http://dx.doi.org/10.4049/jimmunol.181.2.991] [PMID: 18606650]
[44]
Kosinska MK, Liebisch G, Lochnit G, et al. A lipidomic study of phospholipid classes and species in human synovial fluid. Arthritis Rheum 2013; 65(9): 2323-33.
[http://dx.doi.org/10.1002/art.38053] [PMID: 23784884]
[45]
de Munter W, van den Bosch MH, Slöetjes AW, et al. High LDL levels lead to increased synovial inflammation and accelerated ectopic bone formation during experimental osteoarthritis. Osteoarthritis Cartilage 2016; 24(5): 844-55.
[http://dx.doi.org/10.1016/j.joca.2015.11.016] [PMID: 26687826]
[46]
Dennis EA, Norris PC. Eicosanoid storm in infection and inflammation. Nat Rev Immunol 2015; 15(8): 511-23.
[http://dx.doi.org/10.1038/nri3859] [PMID: 26139350]
[47]
Lippiello L, Walsh T, Fienhold M. The association of lipid abnormalities with tissue pathology in human osteoarthritic articular cartilage. Metabolism 1991; 40(6): 571-6.
[http://dx.doi.org/10.1016/0026-0495(91)90046-Y] [PMID: 1865821]
[48]
Tiku ML, Shah R, Allison GT. Evidence linking chondrocyte lipid peroxidation to cartilage matrix protein degradation. Possible role in cartilage aging and the pathogenesis of osteoarthritis. J Biol Chem 2000; 275(26): 20069-76.
[http://dx.doi.org/10.1074/jbc.M907604199] [PMID: 10867027]
[49]
Sano Y, Toyoshima S. Activation of inflammation and resolution pathways of lipid mediators in synovial fluid from patients with severe rheumatoid arthritis compared with severe osteoarthritis 2020; 10(2) e21
[50]
Jónasdóttir HS, Brouwers H, Kwekkeboom JC, et al. Targeted lipidomics reveals activation of resolution pathways in knee osteoarthritis in humans. Osteoarthritis Cartilage 2017; 25(7): 1150-60.
[http://dx.doi.org/10.1016/j.joca.2017.01.018] [PMID: 28189826]
[51]
Woetzel D, Huber R, Kupfer P, et al. Identification of rheumatoid arthritis and osteoarthritis patients by transcriptome-based rule set generation. Arthritis Res Ther 2014; 16(2): R84.
[http://dx.doi.org/10.1186/ar4526] [PMID: 24690414]
[52]
Timur UT, Caron MMJ, Bastiaansen-Jenniskens YM, et al. Celecoxib-mediated reduction of prostanoid release in Hoffa’s fat pad from donors with cartilage pathology results in an attenuated inflammatory phenotype. Osteoarthritis Cartilage 2018; 26(5): 697-706.
[http://dx.doi.org/10.1016/j.joca.2018.01.025] [PMID: 29426013]
[53]
Zhai Q, Dong J. Mesenchymal stem cells enhance therapeutic effect and prevent adverse gastrointestinal reaction of methotrexate treatment in collagen-induced arthritis 2021 2021. 8850820
[54]
Huang R, Wang X, Zhou Y, Xiao Y. RANKL-induced M1 macrophages are involved in bone formation. Bone Res 2017; 5: 17019.
[http://dx.doi.org/10.1038/boneres.2017.19] [PMID: 29263936]
[55]
Petrovic-Rackov L, Pejnovic N. Clinical significance of IL-18, IL-15, IL-12 and TNF-alpha measurement in rheumatoid arthritis. Clin Rheumatol 2006; 25(4): 448-52.
[http://dx.doi.org/10.1007/s10067-005-0106-0] [PMID: 16362448]
[56]
Wada TT, Araki Y, Sato K, et al. Aberrant histone acetylation contributes to elevated interleukin-6 production in rheumatoid arthritis synovial fibroblasts. Biochem Biophys Res Commun 2014; 444(4): 682-6.
[http://dx.doi.org/10.1016/j.bbrc.2014.01.195] [PMID: 24513290]
[57]
Tsuneyoshi Y, Tanaka M, Nagai T, et al. Functional folate receptor beta-expressing macrophages in osteoarthritis synovium and their M1/M2 expression profiles. Scand J Rheumatol 2012; 41(2): 132-40.
[http://dx.doi.org/10.3109/03009742.2011.605391] [PMID: 22211358]
[58]
Kim SJ, Chang HJ, Volin MV, et al. Macrophages are the primary effector cells in IL-7-induced arthritis. Cell Mol Immunol 2020; 17(7): 728-40.
[http://dx.doi.org/10.1038/s41423-019-0235-z] [PMID: 31197255]
[59]
van Leeuwen EM, Sprent J, Surh CD. Generation and maintenance of memory CD4(+) T Cells. Curr Opin Immunol 2009; 21(2): 167-72.
[http://dx.doi.org/10.1016/j.coi.2009.02.005] [PMID: 19282163]
[60]
Kallies A. Distinct regulation of effector and memory T-cell differentiation. Immunol Cell Biol 2008; 86(4): 325-32.
[http://dx.doi.org/10.1038/icb.2008.16] [PMID: 18362944]
[61]
Yu SF, Zhang YN, Yang BY, Wu CY. Human memory, but not naive, CD4+ T cells expressing transcription factor T-bet might drive rapid cytokine production. J Biol Chem 2014; 289(51): 35561-9.
[http://dx.doi.org/10.1074/jbc.M114.608745] [PMID: 25378399]
[62]
Yamada H, Nakashima Y, Okazaki K, et al. Preferential accumulation of activated Th1 cells not only in rheumatoid arthritis but also in osteoarthritis joints. J Rheumatol 2011; 38(8): 1569-75.
[http://dx.doi.org/10.3899/jrheum.101355] [PMID: 21532055]
[63]
Kang YM, Zhang X, Wagner UG, et al. CD8 T cells are required for the formation of ectopic germinal centers in rheumatoid synovitis. J Exp Med 2002; 195(10): 1325-36.
[http://dx.doi.org/10.1084/jem.20011565] [PMID: 12021312]
[64]
Croia C, Serafini B, Bombardieri M, et al. Epstein-Barr virus persistence and infection of autoreactive plasma cells in synovial lymphoid structures in rheumatoid arthritis. Ann Rheum Dis 2013; 72(9): 1559-68.
[http://dx.doi.org/10.1136/annrheumdis-2012-202352] [PMID: 23268369]
[65]
Hussein MR, Fathi NA, El-Din AM, et al. Alterations of the CD4(+), CD8 (+) T cell subsets, interleukins-1beta, IL-10, IL-17, tumor necrosis factor-alpha and soluble intercellular adhesion molecule-1 in rheumatoid arthritis and osteoarthritis: Preliminary observations. Pathol Oncol Res 2008; 14(3): 321-8.
[http://dx.doi.org/10.1007/s12253-008-9016-1] [PMID: 18392953]
[66]
Pawłowska J, Mikosik A, Soroczynska-Cybula M, et al. Different distribution of CD4 and CD8 T cells in synovial membrane and peripheral blood of rheumatoid arthritis and osteoarthritis patients. Folia Histochem Cytobiol 2009; 47(4): 627-32.
[PMID: 20430731]
[67]
György B, Szabó TG, Turiák L, et al. Improved flow cytometric assessment reveals distinct microvesicle (cell-derived microparticle) signatures in joint diseases. PLoS One 2012; 7(11)e49726
[http://dx.doi.org/10.1371/journal.pone.0049726] [PMID: 23185418]
[68]
Deane KD. Preclinical rheumatoid arthritis (autoantibodies): An updated review. Curr Rheumatol Rep 2014; 16(5): 419.
[http://dx.doi.org/10.1007/s11926-014-0419-6] [PMID: 24643396]
[69]
Pessler F, Ogdie AR, Mayer CT, et al. Amyloid arthropathy associated with multiple myeloma: Polyarthritis without synovial infiltration of CD20+ or CD38+ cells. Amyloid 2014; 21(1): 28-34.
[http://dx.doi.org/10.3109/13506129.2013.862229] [PMID: 24286442]
[70]
Cole S, Walsh A, Yin X, et al. Integrative analysis reveals CD38 as a therapeutic target for plasma cell-rich pre-disease and established rheumatoid arthritis and systemic lupus erythematosus. Arthritis Res Ther 2018; 20(1): 85.
[http://dx.doi.org/10.1186/s13075-018-1578-z] [PMID: 29720240]
[71]
Yu M, Cavero V, Lu Q, Li H. Follicular helper T cells in rheumatoid arthritis. Clin Rheumatol 2015; 34(9): 1489-93.
[http://dx.doi.org/10.1007/s10067-015-3028-5] [PMID: 26227164]
[72]
Aldridge J, Ekwall AH, Mark L, et al. T helper cells in synovial fluid of patients with rheumatoid arthritis primarily have a Th1 and a CXCR3+Th2 phenotype. Arthritis Res Ther 2020; 22(1): 245.
[http://dx.doi.org/10.1186/s13075-020-02349-y] [PMID: 33066816]
[73]
Nakayama T, Yoshimura M, Higashioka K, et al. Type 1 helper T cells generate CXCL9/10-producing T-bet+ effector B cells potentially involved in the pathogenesis of rheumatoid arthritis. Cell Immunol 2021; 360104263
[http://dx.doi.org/10.1016/j.cellimm.2020.104263] [PMID: 33387686]
[74]
Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science 2003; 299(5609): 1057-61.
[http://dx.doi.org/10.1126/science.1079490] [PMID: 12522256]
[75]
Massalska M, Radzikowska A, Kuca-Warnawin E, et al. CD4+FOXP3+ T cells in rheumatoid arthritis bone marrow are partially impaired. Cells 2020; 9(3)E549
[http://dx.doi.org/10.3390/cells9030549] [PMID: 32111105]
[76]
Moradi B, Schnatzer P, Hagmann S, et al. CD4+CD25+/high CD127low/− regulatory T cells are enriched in rheumatoid arthritis and osteoarthritis joints-analysis of frequency and phenotype in synovial membrane, synovial fluid and peripheral blood. Arthritis Res Ther 2014; 16(2): R97.
[http://dx.doi.org/10.1186/ar4545] [PMID: 24742142]
[77]
Pillinger MH, Abramson SB. The neutrophil in rheumatoid arthritis. Rheum Dis Clin North Am 1995; 21(3): 691-714.
[http://dx.doi.org/10.1016/S0889-857X(21)00463-4] [PMID: 8619095]
[78]
Haraden CA, Huebner JL, Hsueh MF, Li YJ, Kraus VB. Synovial fluid biomarkers associated with osteoarthritis severity reflect macrophage and neutrophil related inflammation 2019; 21(1): 146.
[http://dx.doi.org/10.1186/s13075-019-1923-x]
[79]
Khandpur R, Carmona-Rivera C, Vivekanandan-Giri A, et al. NETs are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis. Sci Transl Med 2013; 5(178)178ra40
[http://dx.doi.org/10.1126/scitranslmed.3005580] [PMID: 23536012]
[80]
de Lange-Brokaar BJ, Kloppenburg M, Andersen SN, et al. Characterization of synovial mast cells in knee osteoarthritis: Association with clinical parameters. Osteoarthritis Cartilage 2016; 24(4): 664-71.
[http://dx.doi.org/10.1016/j.joca.2015.11.011] [PMID: 26671522]
[81]
Fritz P, Reiser H, Saal JG, Hadam M, Müller J, Wegner G. Analysis of mast cells in rheumatoid arthritis and osteoarthritis by an avidin-peroxidase staining. Virchows Arch B Cell Pathol Incl Mol Pathol 1984; 47(1): 35-45.
[http://dx.doi.org/10.1007/BF02890187] [PMID: 6083657]
[82]
Suurmond J, Rivellese F, Dorjée AL, et al. Toll-like receptor triggering augments activation of human mast cells by anti-citrullinated protein antibodies. Ann Rheum Dis 2015; 74(10): 1915-23.
[http://dx.doi.org/10.1136/annrheumdis-2014-205562] [PMID: 24818634]
[83]
Huangfu N, Zheng W, Xu Z, et al. RBM4 regulates M1 macrophages polarization through targeting STAT1-mediated glycolysis. Int Immunopharmacol 2020; 83106432
[http://dx.doi.org/10.1016/j.intimp.2020.106432] [PMID: 32248017]
[84]
Benigni G, Dimitrova P. CXCR3/CXCL10 axis regulates neutrophil-NK cell cross-talk determining the severity of experimental osteoarthritis. J Immunol 2017; 198: 2115-24.
[85]
Bonfante HL, Almeida CS, Abramo C, Grunewald STF, Levy RA, Teixeira HC. CCL2, CXCL8, CXCL9 and CXCL10 serum levels increase with age but are not altered by treatment with hydroxychloroquine in patients with osteoarthritis of the knees. Int J Rheum Dis 2017; 20(12): 1958-64.
[http://dx.doi.org/10.1111/1756-185X.12589] [PMID: 25955863]
[86]
Dai M, Liu X, Wang N, Sun J. Squid type II collagen as a novel biomaterial: Isolation, characterization, immunogenicity and relieving effect on degenerative osteoarthritis via inhibiting STAT1 signaling in pro-inflammatory macrophages. Mater Sci Eng C 2018; 89: 283-94.
[http://dx.doi.org/10.1016/j.msec.2018.04.021] [PMID: 29752100]
[87]
Burris HA, Infante JR, Ansell SM, et al. Safety and activity of varlilumab, a novel and first-in-class agonist anti-CD27 antibody, in patients with advanced solid tumors. J Clin Oncol 2017; 35(18): 2028-36.
[http://dx.doi.org/10.1200/JCO.2016.70.1508] [PMID: 28463630]
[88]
Berning P, Schaefer C, Clemens D, Korsching E, Dirksen U. The CXCR4 antagonist plerixafor (AMD3100) promotes proliferation of Ewing sarcoma cell lines in vitro and activates receptor tyrosine kinase signaling. Cell Commun Signal 2018; 16(1): 21.

Rights & Permissions Print Cite
Article Metrics
82
1
Wayfinder Image
Open Access Journals Promotions
World Antimicrobial Awareness Week
© 2024 Bentham Science Publishers | Privacy Policy