{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T02:13:30Z","timestamp":1780107210058,"version":"3.54.0"},"reference-count":60,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,1,30]],"date-time":"2021-01-30T00:00:00Z","timestamp":1611964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004442","name":"National Science Centre, Poland","doi-asserted-by":"publisher","award":["2016\/21\/B\/NZ5\/00500"],"award-info":[{"award-number":["2016\/21\/B\/NZ5\/00500"]}],"id":[{"id":"10.13039\/501100004442","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The domination of pro-inflammatory Th subsets (Th1, Th17) is characteristic of ankylosing spondylitis (AS). Mesenchymal stem cells (MSC) were reported to normalize Th imbalance, but whether MSCs from AS adipose tissue (AS\/ASCs) possess such properties is unknown. We examined AS\/ASCs\u2019 impact on Th-cell differentiation, using healthy donors ASCs (HD\/ASCs) as a control. The assessment of the expression of transcription factors defining Th1 (T-bet), Th2 (GATA3), Th17 (RORc), and Treg (FoxP3) subsets by quantitative RT-PCR, the concentrations of subset-specific cytokines by ELISA, and Treg (CD4+CD25highFoxP3+) formation by flow cytometry, were performed in the co-cultures of ASCs with activated CD4+ T cells or peripheral blood mononuclear cells (PBMCs). AS\/ASCs and HD\/ASCs exerted similar immunomodulatory effects. Acting directly on CD4+ T cells, ASCs decreased the T-bet\/GATA3 and RORc\/FoxP3 ratios, diminished Treg formation, but increase IFN\u03b3 and IL-17AF production, while ASCs co-cultured with PBMCs enhanced Treg generation and reduced IFN\u03b3 release. ASCs failed to up-regulate the anti-inflammatory IL-10 and TGF\u03b2. AS\/ASCs\u2019 impact on allogeneic and autologous PBMCs was similar. In conclusion, to shift Th differentiation to a functional anti-inflammatory direction, ASCs require accessory cell support, whereas their direct effect may be pro-inflammatory. Because ASCs neither inhibit IL-17AF nor up-regulate anti-inflammatory cytokines, their usefulness for AS patients\u2019 treatment remains uncertain.<\/jats:p>","DOI":"10.3390\/cells10020280","type":"journal-article","created":{"date-parts":[[2021,1,30]],"date-time":"2021-01-30T08:56:01Z","timestamp":1611996961000},"page":"280","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Modulatory Impact of Adipose-Derived Mesenchymal Stem Cells of Ankylosing Spondylitis Patients on T Helper Cell Differentiation"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9068-3885","authenticated-orcid":false,"given":"Ewa","family":"Kuca-Warnawin","sequence":"first","affiliation":[{"name":"Department of Pathophysiology and Immunology, National Institute of Geriatrics, Rheumatology, and Rehabilitation, 02-637 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iwona","family":"Janicka","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Immunology, National Institute of Geriatrics, Rheumatology, and Rehabilitation, 02-637 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krzysztof","family":"Bonek","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, National Institute of Geriatrics, Rheumatology, and Rehabilitation, 02-637 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"Kontny","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Immunology, National Institute of Geriatrics, Rheumatology, and Rehabilitation, 02-637 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S0140-6736(16)31591-4","article-title":"Axial spondyloarthritis","volume":"390","author":"Sieper","year":"2017","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7146","DOI":"10.1038\/ncomms8146","article-title":"Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1","volume":"6","author":"Cortes","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.biopha.2018.01.108","article-title":"Immune cells involved in the pathogenesis of ankylosing spondylitis","volume":"100","author":"Rezaiemanesh","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.3389\/fimmu.2018.01610","article-title":"Increased IL-22 and IL-17A-producing mucosal-associated invariant T cells in the peripheral blood of patients with ankylosing spondylitis","volume":"9","author":"Toussirot","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"885","DOI":"10.3389\/fimmu.2018.00885","article-title":"Whodunit? The contribution of interleukin(IL)-17\/IL-22-producing \u03b3\u03b4 T cells, \u03b1\u03b2 T cells, and innate lymphoid cells to the pathogenesis of spondyloarthritis","volume":"9","author":"Reinhardt","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1136\/annrheumdis-2016-210023","article-title":"Secukinumab efficacy in anti-TNF-na\u00efve and anti-TNF-experienced subjects with active ankylosing spondylitis; results from the MEASURE 2 study","volume":"76","author":"Sieper","year":"2017","journal-title":"Ann. Rheum. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Wen, J.T., Zhang, D.H., Fang, P.F., Li, M.H., Wang, R.J., and Li, S.H. (2017). Role of Th1\/Th2 cytokines in the diagnosis and prognostic evaluation of ankylosing spondylitis. Genet. Mol. Res., 16.","DOI":"10.4238\/gmr16019322"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"250","DOI":"10.3892\/etm.2014.2046","article-title":"T lymphocytes subset imbalances in patients contribute to ankylosing spondylitis","volume":"9","author":"Wang","year":"2015","journal-title":"Exp. Ther. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"69","DOI":"10.5582\/bst.2016.01171","article-title":"The immune dysfunction in ankylosing spondylitis patients","volume":"11","author":"Duan","year":"2017","journal-title":"Biosci. Trends"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2307","DOI":"10.1002\/art.23655","article-title":"Increased numbers of circulating polyfunctional Th17 memory cells in patients with seronegative spondyloarthritides","volume":"58","author":"Jandus","year":"2008","journal-title":"Arthritis Rheum."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1007\/s11926-018-0729-1","article-title":"Functional defects of Treg cells: New targets in rheumatic diseases, including ankylosing spondylitis","volume":"20","author":"Miao","year":"2018","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.intimp.2018.03.032","article-title":"Dysfunction of regulatory T cells in patients with ankylosing spondylitis is associated with a loss of Tim-3","volume":"59","author":"Wang","year":"2018","journal-title":"Int. Immunopharmacol."},{"key":"ref_13","first-page":"2","article-title":"Immunomodulation by mesenchymal stromal cells and their clinical application","volume":"3","author":"Cagliani","year":"2017","journal-title":"J. Stem Cell Regen. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/scrt75","article-title":"Mesenchymal stem cell effects on T-cell effector pathways","volume":"2","author":"Duffy","year":"2011","journal-title":"Stem Cell Res. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"913050","DOI":"10.1155\/2014\/913050","article-title":"Whole genome expression profiling and signal pathway screening of MSCs in ankylosing spondylitis","volume":"2014","author":"Li","year":"2014","journal-title":"Stem Cells Int."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/s00109-016-1489-x","article-title":"MCP1 triggers monocyte dysfunctions during abnormal osteogenic differentiation of mesenchymal stem cells in ankylosing spondylitis","volume":"95","author":"Xie","year":"2017","journal-title":"J. Mol. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/ar3257","article-title":"Reduced immunomodulation potential of bone marrow-derived mesenchymal stem cells induced CCR4+CCR6+ Th\/Treg cell subset imbalance in ankylosing spondylitis","volume":"13","author":"Wu","year":"2011","journal-title":"Arthritis Res. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Krajewska-W\u0142odarczyk, M., Owczarczyk-Saczonek, A., Placek, W., Osowski, A., Engelgardt, P., and Wojtkiewicz, J. (2018). Role of stem cells in pathophysiology and therapy of spondyloarthropathies\u2014New therapeutic possibilities?. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19010080"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1186\/s13256-018-1776-y","article-title":"Ankylosing spondylitis, chronic fatigue, and depression improve after stromal vascular fraction treatment for osteoarthritis: A case report","volume":"12","author":"Bright","year":"2018","journal-title":"J. Med. Case Rep."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Kuca-Warnawin, E., Skalska, U., Janicka, I., Musia\u0142owicz, U., Bonek, K., G\u0142uszko, P., Szcz\u0119sny, P., Olesi\u0144ska, M., and Kontny, E. (2019). The phenotype and secretory activity of adipose-derived mesenchymal stem cells (ASCs) of patients with rheumatic diseases. Cells, 8.","DOI":"10.3390\/cells8121659"},{"key":"ref_21","first-page":"1","article-title":"Modulation of T-cell activation markers expression by the adipose tissue-derived mesenchymal stem cells of patients with rheumatic diseases","volume":"29","author":"Janicka","year":"2020","journal-title":"Cell Transplant."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1136\/ard.2009.108233","article-title":"The development of Assessment of SpondyloArthritis international Society classification criteria for axial spoandyloarthritis (part II): Validation and final selection","volume":"68","author":"Rudwaleit","year":"2009","journal-title":"Ann. Rheum. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1093\/rheumatology\/kes129","article-title":"Intra-articular adipose-derived mesenchymal stem cells from rheumatoid arthritis patients maintain the function of chondrogenic differentiation","volume":"51","author":"Skalska","year":"2012","journal-title":"Rheumatology (Oxford)"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1111\/j.1600-065X.2010.00951.x","article-title":"Peripheral CD4+ T-cell differentiation regulated by networks of cytokines and transcription factors","volume":"238","author":"Zhu","year":"2010","journal-title":"Immmunol. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Lee, G.R. (2018). The balance of Th17 versus Treg cells in autoimmunity. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19030730"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1186\/s13075-020-02226-8","article-title":"TNF-\u03b1 inhibitor therapy can improve the immune imbalance of CD4+ T cells and negative regulatory cells but not CD8+ T cells in ankylosing spondylitis","volume":"22","author":"Yang","year":"2020","journal-title":"Arthritis Res. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1002\/art.24568","article-title":"Frequency and phenotype of peripheral blood Th17 cells in ankylosing spondylitis and rheumatoid arthritis","volume":"60","author":"Shen","year":"2009","journal-title":"Arthritis Rheum."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.biopha.2018.02.059","article-title":"Oral administration effects of \u03b2-D-mannuronic acid (M2000) on Th17 and regulatory T cells in patients with ankylosing spondylitis","volume":"100","author":"Fattahi","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s10875-012-9774-0","article-title":"Levels of circulating Th17 cells and regulatory T cells in ankylosing spondylitis patients with an inadequate response to anti- TNF \u2013\u03b1 therapy","volume":"33","author":"Li","year":"2013","journal-title":"J. Clin. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1894","DOI":"10.3389\/fimmu.2020.01894","article-title":"Bimekizumab, a novel humanized IgG1 antibody that neutralizes both IL-17A and IL-17F","volume":"11","author":"Adams","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.2147\/CIA.S259762","article-title":"Human adipose tissue-derived mesenchymal stem cells in Parkinson\u2019s Disease: Inhibition of T helper 17 cell differentiation and regulation of immune balance towards a regulatory cell phenotype","volume":"15","author":"Bi","year":"2020","journal-title":"Clin. Interv. Aging"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Fasching, P., Stadner, M., Graninger, W., Dejaco, C., and Fessler, J. (2017). Therapeutic potential of targeting the Th17\/Treg axis in autoimmune disorders. Molecules, 22.","DOI":"10.3390\/molecules22010134"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1093\/bfgp\/elt025","article-title":"Transcriptional factor interplay in T helper cell differentiation","volume":"12","author":"Evans","year":"2013","journal-title":"Brief. Funct. Genom."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1111\/imm.12216","article-title":"Transcriptional regulation of T helper type 2 differentiation","volume":"141","author":"Lee","year":"2013","journal-title":"Immunology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/j.intimp.2010.11.008","article-title":"FoxP3 and ROR\u03b3\u03c4: Transcriptional regulation of Treg and Th17","volume":"11","author":"Chen","year":"2011","journal-title":"Int. Immunopharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1007\/s10875-019-00684-7","article-title":"Regulatory T cells: The many faces of FoxP3","volume":"39","author":"Georgiev","year":"2019","journal-title":"J. Clin. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Seo, Y., Shin, T.H., and Kim, H.S. (2019). Current strategies to enhance adipose stem cell function: An update. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20153827"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"21145","DOI":"10.1002\/jcp.28717","article-title":"Th17 immune response to adipose tissue-derived mesenchymal stromal cells","volume":"234","author":"Najar","year":"2019","journal-title":"J. Cell Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/s00011-018-1205-0","article-title":"Immunological modulation following bone marrow-derived mesenchymal stromal cells and Th17 lymphocyte co-cultures","volume":"68","author":"Najar","year":"2019","journal-title":"Inflamm. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"725","DOI":"10.4049\/jimmunol.1601808","article-title":"mPGES1-dependent prostaglandin E2 (PGE2) controls antigen-specific Th17 and Th1 responses by regulating T autocrine and paracrine PGE2 production","volume":"200","author":"Maseda","year":"2018","journal-title":"J. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"35521","DOI":"10.1038\/srep35521","article-title":"Interferon regulatory factor 4 controls Th1 cell effector function and metabolism","volume":"6","author":"Mahnke","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2840","DOI":"10.1002\/eji.200839070","article-title":"Fetal BM-derived mesenchymal stem cells promote the expansion of human Th17 cells, but inhibit the production of Th1 cells","volume":"39","author":"Guo","year":"2009","journal-title":"Eur. J. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.imlet.2010.09.006","article-title":"Opposing effect of mesenchymal stem cells on Th1 and Th17 cell polarization according to the state of CD4+ T cell activation","volume":"135","author":"Nova","year":"2011","journal-title":"Immunol. Lett."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1002\/ana.22065","article-title":"Reciprocal Th1 and Th17 regulation by mesenchymal stem cells: Implication for multiple sclerosis","volume":"68","author":"Darlington","year":"2010","journal-title":"Ann. Neurol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.5966\/sctm.2015-0243","article-title":"Human mesenchymal stem cells impact Th17 and Th1 responses through a prostaglandin E2 and myeloid-dependent mechanism","volume":"5","author":"Rozenberg","year":"2016","journal-title":"Stem Cells Transl. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1980","DOI":"10.1002\/stem.1432","article-title":"Multipotent stromal cells induce human regulatory T cells through a novel pathway involving skewing of monocytes toward anti-inflammatory macrophages","volume":"31","author":"Melief","year":"2013","journal-title":"Stem Cells"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/scrt216","article-title":"Mesenchymal stem cells generate a CD4+CD25+ Foxp3+ regulatory T cell population during the differentiation process of Th1 and Th17 cells","volume":"4","author":"Kurte","year":"2013","journal-title":"Stem Cell Res. Ther."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Luz-Crawford, P., No\u00ebl, D., Fernandez, X., Khoury, M., Figueroa, F., Carri\u00f2n, F., Jorgense, C., and Djouad, F. (2012). Mesenchymal stem cells repress Th17 molecular program through the PD-1 pathway. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0045272"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/scrt537","article-title":"Effect of human bone marrow mesenchymal stromal cells on cytokine production by peripheral blood na\u00efve, memory, and effector T cells","volume":"6","author":"Laranjeira","year":"2015","journal-title":"Stem Cell Res. Ther."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"302","DOI":"10.4049\/jimmunol.0902007","article-title":"Mesenchymal stem cells inhibit human Th17 cell differentiation and function and induce a T regulatory cell phenotype","volume":"185","author":"Ghannam","year":"2010","journal-title":"J. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2840","DOI":"10.1002\/eji.201141499","article-title":"Mesenchymal stem cell inhibition of T-helper 17 cell-differentiation is triggered by cell-cell contact and mediated by prostaglandin E2 via EP4 receptor","volume":"41","author":"Duffy","year":"2011","journal-title":"Eur. J. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"686","DOI":"10.3109\/14653249.2010.542456","article-title":"Mesenchymal stromal cells inhibit Th17 but not regulatory T-cell differentiation","volume":"13","author":"Tatara","year":"2011","journal-title":"Cytotherapy"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1016\/j.celrep.2017.10.090","article-title":"Reciprocal expression of IL-35 and IL-10 defines two distinct effector Treg subsets that are required for maintenance of immune tolerance","volume":"21","author":"Wei","year":"2017","journal-title":"Cell Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1016\/j.immuni.2018.12.001","article-title":"The biology of T regulatory type 1 cells and their therapeutic application in immune-mediated diseases","volume":"49","author":"Roncarolo","year":"2018","journal-title":"Immunity"},{"key":"ref_55","first-page":"295167","article-title":"Conditioned medium from adipose tissue-derived mesenchymal stem cells induces CD4+FOXP3+ cells and increases IL-10 secretion","volume":"2012","author":"Bochev","year":"2012","journal-title":"J. Biomed. Biotechnol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1111\/cei.12120","article-title":"Human adipose-tissue derived mesenchymal stem cells induce functional de novo regulatory T cells with methylated FOXP3 gene DNA","volume":"173","author":"Engela","year":"2013","journal-title":"Clin. Exp. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.imbio.2012.02.007","article-title":"Mesenchymal stem cells promote neutrophil activation by inducing IL-17 production in CD4+ CD45RO+ T cells","volume":"218","author":"Hsu","year":"2013","journal-title":"Immunobiology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1084\/jem.20060468","article-title":"Expression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T cells","volume":"203","author":"Seddiki","year":"2006","journal-title":"J. Exp. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1136\/ard.2007.076174","article-title":"Functional, molecular and proteomic characterisation of bone marrow mesenchymal stem cells in rheumatoid arthritis","volume":"67","author":"Kastrianaki","year":"2008","journal-title":"Ann. Rheum. Dis."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1042\/CBI20090211","article-title":"Effects of non-steroidal anti-inflammatory drugs on proliferation, differentiation and migration in equine mesenchymal stem cells","volume":"35","author":"Raabe","year":"2011","journal-title":"Cell Biol. 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