{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T12:50:34Z","timestamp":1763643034265,"version":"3.41.2"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,12,4]],"date-time":"2020-12-04T00:00:00Z","timestamp":1607040000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Cytokine cascades exist in many autoimmune disorders which amplify and sustain the autoimmune process and lead to chronic inflammatory injury to the host tissues. Increasing evidence indicates that chondrocytes can interact with T cells, which may be a crucial event in inflammatory arthritis. To address the reciprocal influences of cartilage-reactive T cells and chondrocytes, we constructed cartilage-reactive T cells by developing a type II collagen-specific chimeric antigen receptor (CII-CAR). An<jats:italic>in vitro<\/jats:italic>co-culture model of CII-CAR-T cells and fresh cartilage was developed, in which CII-CAR-T displayed specific proliferative capacity and cytokine release against fresh cartilage samples, and chondrocytes could respond to CII-CAR-T cells by secreting IL-6. The proposed model will help us to explore the possible cytokine cascades between cartilage-reactive T cells and cartilage.<\/jats:p>","DOI":"10.3389\/fimmu.2020.568741","type":"journal-article","created":{"date-parts":[[2020,12,4]],"date-time":"2020-12-04T04:59:40Z","timestamp":1607057980000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Construction of CII-Specific CAR-T to Explore the Cytokine Cascades Between Cartilage-Reactive T Cells and Chondrocytes"],"prefix":"10.3389","volume":"11","author":[{"given":"Xiaolong","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ce","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiyu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongtao","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junlong","family":"Dang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongguang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia","family":"Wei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liqing","family":"Kang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fenglin","family":"Cao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Song Guo","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenkun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2020,12,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.015099","article-title":"Restoring the balance: immunotherapeutic combinations for autoimmune disease","volume":"7","author":"Smilek","year":"2014","journal-title":"Dis Model Mech"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.02.006","article-title":"Immunopathogenesis of Rheumatoid Arthritis","volume":"46","author":"Firestein","year":"2017","journal-title":"Immunity"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1172\/JCI97965","article-title":"Long noncoding RNA LERFS negatively regulates rheumatoid synovial aggression and proliferation","volume":"128","author":"Zou","year":"2018","journal-title":"J Clin Invest"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3390\/cells7100161","article-title":"Pathogenic Role of Immune Cells in Rheumatoid Arthritis: Implications in Clinical Treatment and Biomarker Development","volume":"7","author":"Yap","year":"2018","journal-title":"Cells"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2019.11.024","article-title":"LncRNA PICSAR promotes cell proliferation, migration and invasion of fibroblast-like synoviocytes by sponging miRNA-4701-5p in rheumatoid arthritis","volume":"50","author":"Bi","year":"2019","journal-title":"EBioMedicine"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2011-201052","article-title":"Induced T regulatory cells suppress osteoclastogenesis and bone erosion in collagen-induced arthritis better than natural T regulatory cells","volume":"71","author":"Kong","year":"2012","journal-title":"Ann Rheum Dis"},{"key":"B7","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.1186\/ar2412","article-title":"T cells in rheumatoid arthritis","volume":"10","author":"Cope","year":"2008","journal-title":"Arthritis Res Ther"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1002\/art.41189","article-title":"Peptidyl arginine deiminase autoimmunity and the development of ACPA in rheumatoid arthritis. The \u201chapten carrier\u201d model","volume":"72","author":"Auger","year":"2019","journal-title":"Arthritis Rheumatol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1800421","article-title":"In Rheumatoid Arthritis, Synovitis at Different Inflammatory Sites Is Dominated by Shared but Patient-Specific T Cell Clones","volume":"201","author":"Musters","year":"2018","journal-title":"J Immunol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.33594\/000000080","article-title":"Helios but not CD226, TIGIT and Foxp3 is a Potential Marker for CD4(+) Treg Cells in Patients with Rheumatoid Arthritis","volume":"52","author":"Yang","year":"2019","journal-title":"Cell Physiol Biochem"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2019.03.008","article-title":"T-cells interact with B cells, dendritic cells, and fibroblast-like synoviocytes as hub-like key cells in rheumatoid arthritis","volume":"70","author":"Hu","year":"2019","journal-title":"Int Immunopharmacol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1501740","article-title":"TGF-beta-Induced Regulatory T Cells Directly Suppress B Cell Responses through a Noncytotoxic Mechanism","volume":"196","author":"Xu","year":"2016","journal-title":"J Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2013.12.011","article-title":"The function of BAFF on T helper cells in autoimmunity","volume":"25","author":"Chen","year":"2014","journal-title":"Cytokine Growth Factor Rev"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1201029","article-title":"Dendritic cell-specific disruption of TGF-beta receptor II leads to altered regulatory T cell phenotype and spontaneous multiorgan autoimmunity","volume":"189","author":"Ramalingam","year":"2012","journal-title":"J Immunol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1002\/art.41182","article-title":"Role of Chondrocytes in the Development of Rheumatoid Arthritis Via Transmembrane Protein 147-Mediated NF-kappaB Activation","volume":"72","author":"Ota","year":"2020","journal-title":"Arthritis Rheumatol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1126\/science.aar6711","article-title":"CAR T cell immunotherapy for human cancer","volume":"359","author":"June","year":"2018","journal-title":"Science"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1126\/science.aat0962","article-title":"Refining cell therapy","volume":"359","author":"Roybal","year":"2018","journal-title":"Science"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.15644","article-title":"Cytokine release syndrome and neurotoxicity after CD19 chimeric antigen receptor-modified (CAR-) T cell therapy","volume":"183","author":"Hay","year":"2018","journal-title":"Br J Haematol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/322547a0","article-title":"Tumour necrosis factor alpha stimulates resorption and inhibits synthesis of proteoglycan in cartilage","volume":"322","author":"Saklatvala","year":"1986","journal-title":"Nature"},{"key":"B20","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1038\/s41419-018-1266-6","article-title":"Differential roles of TNFalpha-TNFR1 and TNFalpha-TNFR2 in the differentiation and function of CD4(+)Foxp3(+) induced Treg cells in vitro and in vivo periphery in autoimmune diseases","volume":"10","author":"Yang","year":"2019","journal-title":"Cell Death Dis"},{"key":"B21","doi-asserted-by":"publisher","first-page":"e0455","DOI":"10.1097\/MD.0000000000010455","article-title":"Arthritis of large joints shown as a rare clinical feature of cytokine release syndrome after chimeric antigen receptor T cell therapy: A case report","volume":"97","author":"Wang","year":"2018","journal-title":"Medicine (Baltimore)"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19030677","article-title":"Targeting IgG in Arthritis: Disease Pathways and Therapeutic Avenues","volume":"19","author":"Nandakumar","year":"2018","journal-title":"Int J Mol Sci"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780391015","article-title":"Antibodies to type II collagen in early rheumatoid arthritis. Correlation with disease progression","volume":"39","author":"Cook","year":"1996","journal-title":"Arthritis Rheum"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00178","article-title":"1,25-Dihydroxyvitamin D3 Ameliorates Collagen-Induced Arthritis via Suppression of Th17 Cells Through miR-124 Mediated Inhibition of IL-6 Signaling","volume":"10","author":"Zhou","year":"2019","journal-title":"Front Immunol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1172\/JCI36389","article-title":"Evidence that cytokines play a role in rheumatoid arthritis","volume":"118","author":"Brennan","year":"2008","journal-title":"J Clin Invest"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1002\/jor.23043","article-title":"Influence of osteoarthritis grade on molecular signature of human cartilage","volume":"34","author":"Zhou","year":"2016","journal-title":"J Orthop Res"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1302\/0301-620X.43B4.752","article-title":"The etiology of chondromalacia patellae","author":"Outerbridge","year":"1961","journal-title":"J Bone Joint Surg Br"},{"key":"B28","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1053\/joca.2000.0417","article-title":"How severe must repetitive loading be to kill chondrocytes in articular cartilage","volume":"9","author":"Clements","year":"2001","journal-title":"Osteoarthritis Cartilage"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2016.04.016","article-title":"Enhanced phagocytic capacity endows chondrogenic progenitor cells with a novel scavenger function within injured cartilage","volume":"24","author":"Zhou","year":"2016","journal-title":"Osteoarthritis Cartilage"},{"key":"B30","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/1479-5876-10-29","article-title":"Protein L: a novel reagent for the detection of chimeric antigen receptor (CAR) expression by flow cytometry","volume":"10","author":"Zheng","year":"2012","journal-title":"J\u00a0Transl Med"},{"key":"B31","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1038\/nrrheum.2016.193","article-title":"Immune resolution mechanisms in inflammatory arthritis","volume":"13","author":"Perretti","year":"2017","journal-title":"Nat Rev Rheumatol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2012.00077","article-title":"Inflammation and bone destruction in arthritis: synergistic activity of immune and mesenchymal cells in joints","volume":"3","author":"Komatsu","year":"2012","journal-title":"Front Immunol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-019-0219-5","article-title":"HLA associations in inflammatory arthritis: emerging mechanisms and clinical implications","volume":"15","author":"Busch","year":"2019","journal-title":"Nat Rev Rheumatol"},{"key":"B34","article-title":"Pathologic finding of increased expression of interleukin-17 in the synovial tissue of rheumatoid arthritis patients","volume":"6","author":"Li","year":"2013","journal-title":"Int J Clin Exp Pathol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1186\/ar2292","article-title":"Cells of the synovium in rheumatoid arthritis. Chondrocytes","volume":"9","author":"Otero","year":"2007","journal-title":"Arthritis Res Ther"},{"key":"B36","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/S1063-4584(10)60038-6","article-title":"Leptin enhances MMP-1, MMP-3 and MMP-13 production in human osteoarthritic cartilage and correlates with MMP-1 and MMP-3 in synovial fluid from OA patients","volume":"29","author":"Koskinen","year":"2011","journal-title":"Clin Exp Rheumatol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1159\/000488227","article-title":"E74-Like Factor (ELF3) and Leptin, a Novel Loop Between Obesity and Inflammation Perpetuating a Pro-Catabolic State in Cartilage","volume":"45","author":"Conde","year":"2018","journal-title":"Cell Physiol Biochem"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21031071","article-title":"Dual Role of Chondrocytes in Rheumatoid Arthritis: The Chicken and the Egg","volume":"21","author":"Tseng","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00415","article-title":"Human Articular Chondrocytes Regulate Immune Response by Affecting Directly T Cell Proliferation and Indirectly Inhibiting Monocyte Differentiation to Professional Antigen-Presenting Cells","volume":"7","author":"Pereira","year":"2016","journal-title":"Front Immunol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1177\/1941738109350438","article-title":"The basic science of articular cartilage: structure, composition, and function","volume":"1","author":"Sophia Fox","year":"2009","journal-title":"Sports Health"},{"key":"B41","article-title":"Modulation of proinflammatory cytokine release in rheumatoid synovial membrane cell cultures. Comparison of monoclonal anti TNF-alpha antibody with the interleukin-1 receptor antagonist","volume":"6","author":"Butler","year":"1995","journal-title":"Eur Cytokine Netw"},{"key":"B42","doi-asserted-by":"crossref","DOI":"10.4049\/jimmunol.146.10.3365","article-title":"Cytokines in chronic inflammatory arthritis. VI. Analysis of the synovial cells involved in granulocyte-macrophage colony-stimulating factor production and gene expression in rheumatoid arthritis and its regulation by IL-1 and tumor necrosis factor-alpha","volume":"146","author":"Alvaro-Gracia","year":"1991","journal-title":"J Immunol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830211039","article-title":"Expression of granulocyte-macrophage colony-stimulating factor in rheumatoid arthritis: regulation by tumor necrosis factor-alpha","volume":"21","author":"Haworth","year":"1991","journal-title":"Eur J Immunol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/nri802","article-title":"Development of anti-TNF therapy for rheumatoid arthritis","volume":"2","author":"Feldmann","year":"2002","journal-title":"Nat Rev Immunol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1014557107","article-title":"Tumor necrosis factor-alpha triggers a cytokine cascade yielding postoperative cognitive decline","volume":"107","author":"Terrando","year":"2010","journal-title":"Proc Natl Acad Sci USA"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/12.5.659","article-title":"Cartilage-reactive T cells in rheumatoid synovium","volume":"12","author":"Fang","year":"2000","journal-title":"Int Immunol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-017-0619-z","article-title":"Selected cytokine pathways in rheumatoid arthritis","volume":"39","author":"Noack","year":"2017","journal-title":"Semin Immunopathol"},{"key":"B48","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/rheumatology\/kep329","article-title":"Therapeutic targets in rheumatoid arthritis: the interleukin-6 receptor","volume":"49","author":"Dayer","year":"2010","journal-title":"Rheumatol (Oxford)"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.11.7112","article-title":"Cutting edge: Foxp3+CD4+CD25+ regulatory T cells induced by IL-2 and TGF-beta are resistant to Th17 conversion by IL-6","volume":"180","author":"Zheng","year":"2008","journal-title":"J\u00a0Immunol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1408780111","article-title":"Critical role of all-trans retinoic acid in stabilizing human natural regulatory T cells under inflammatory conditions","volume":"111","author":"Lu","year":"2014","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00604","article-title":"Hall of Fame among Pro-inflammatory Cytokines: Interleukin-6 Gene and Its Transcriptional Regulation Mechanisms","volume":"7","author":"Luo","year":"2016","journal-title":"Front Immunol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.4828","article-title":"The pathological and physiological roles of IL-6 amplifier activation","volume":"8","author":"Murakami","year":"2012","journal-title":"Int J Biol Sci"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2011.00022","article-title":"A four-step model for the IL-6 amplifier, a regulator of chronic inflammations in tissue-specific MHC class II-associated autoimmune diseases","volume":"2","author":"Murakami","year":"2011","journal-title":"Front Immunol"},{"key":"B54","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1111\/cei.12966","article-title":"The role of interleukin-6 signalling and its therapeutic blockage in skewing the T cell balance in rheumatoid arthritis","volume":"189","author":"Schinnerling","year":"2017","journal-title":"Clin Exp Immunol"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1080\/14397595.2018.1546357","article-title":"IL-6 inhibitor for the treatment of rheumatoid arthritis: A comprehensive review","volume":"29","author":"Ogata","year":"2019","journal-title":"Mod Rheumatol"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02359","article-title":"Chimeric Antigen Receptor (CAR) Treg: A Promising Approach to Inducing Immunological Tolerance","volume":"9","author":"Zhang","year":"2018","journal-title":"Front Immunol"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00792","article-title":"Prospects of the Use of Cell Therapy to Induce Immune Tolerance","volume":"11","author":"Wang","year":"2020","journal-title":"Front Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2020.568741\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,14]],"date-time":"2023-10-14T15:27:29Z","timestamp":1697297249000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2020.568741\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,4]]},"references-count":57,"alternative-id":["10.3389\/fimmu.2020.568741"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2020.568741","relation":{},"ISSN":["1664-3224"],"issn-type":[{"type":"electronic","value":"1664-3224"}],"subject":[],"published":{"date-parts":[[2020,12,4]]},"article-number":"568741"}}