{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T23:54:26Z","timestamp":1790121266011,"version":"4.0.1"},"reference-count":65,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2015,5,12]],"date-time":"2015-05-12T00:00:00Z","timestamp":1431388800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2015,5,12]],"date-time":"2015-05-12T00:00:00Z","timestamp":1431388800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Dendritic cells (DCs) are critical for immune homeostasis. To target DCs, we generated a mouse line with\n                    <jats:italic>Flip<\/jats:italic>\n                    deficiency in cells that express cre under the CD11c promoter (CD11c-Flip-KO). CD11c-Flip-KO mice spontaneously develop erosive, inflammatory arthritis, resembling rheumatoid arthritis, which is dramatically reduced when these mice are crossed with\n                    <jats:italic>Rag<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/<\/jats:italic>\n                      \u2212\n                    <\/jats:sup>\n                    mice. The CD8\u03b1\n                    <jats:sup>+<\/jats:sup>\n                    DC subset is significantly reduced, along with alterations in NK cells and macrophages. Autoreactive CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells and autoantibodies specific for joint tissue are present, and arthritis severity correlates with the number of autoreactive CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells and plasmablasts in the joint-draining lymph nodes. Reduced T regulatory cells (Tregs) inversely correlate with arthritis severity, and the transfer of Tregs ameliorates arthritis. This KO line identifies a model that will permit in depth interrogation of the pathogenesis of rheumatoid arthritis, including the role of CD8\u03b1\n                    <jats:sup>+<\/jats:sup>\n                    DCs and other cells of the immune system.\n                  <\/jats:p>","DOI":"10.1038\/ncomms8086","type":"journal-article","created":{"date-parts":[[2015,5,12]],"date-time":"2015-05-12T06:40:31Z","timestamp":1431412831000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["CD11c-mediated deletion of Flip promotes autoreactivity and inflammatory arthritis"],"prefix":"10.1038","volume":"6","author":[{"given":"Qi-Quan","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harris","family":"Perlman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Birkett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1019-6783","authenticated-orcid":false,"given":"Renee","family":"Doyle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deyu","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. Kenneth","family":"Haines","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Robinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syamal","family":"Datta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan-Zhen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyewon","family":"Phee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard M.","family":"Pope","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,5,12]]},"reference":[{"key":"BFncomms8086_CR1","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1038\/nri1996","volume":"7","author":"K Shortman","year":"2007","unstructured":"Shortman, K. & Naik, S. H. Steady-state and inflammatory dendritic-cell development. Nat. Rev. Immunol. 7, 19\u201330 (2007).","journal-title":"Nat. Rev. Immunol."},{"key":"BFncomms8086_CR2","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1038\/nri3477","volume":"13","author":"D Ganguly","year":"2013","unstructured":"Ganguly, D., Haak, S., Sisirak, V. & Reizis, B. The role of dendritic cells in autoimmunity. Nat. Rev. Immunol. 13, 566\u2013577 (2013).","journal-title":"Nat. Rev. Immunol."},{"key":"BFncomms8086_CR3","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1038\/nri3149","volume":"12","author":"GT Belz","year":"2012","unstructured":"Belz, G. T. & Nutt, S. L. Transcriptional programming of the dendritic cell network. Nat. Rev. Immunol. 12, 101\u2013113 (2012).","journal-title":"Nat. Rev. Immunol."},{"key":"BFncomms8086_CR4","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1084\/jem.20041457","volume":"200","author":"AM Gallegos","year":"2004","unstructured":"Gallegos, A. M. & Bevan, M. J. Central tolerance to tissue-specific antigens mediated by direct and indirect antigen presentation. J. Exp. Med. 200, 1039\u20131049 (2004).","journal-title":"J. Exp. Med."},{"key":"BFncomms8086_CR5","doi-asserted-by":"publisher","first-page":"2544","DOI":"10.1002\/eji.201041374","volume":"41","author":"C Dresch","year":"2011","unstructured":"Dresch, C. et al. Thymic but not splenic CD8(+) DCs can efficiently cross-prime T cells in the absence of licensing factors. Eur. J. Immunol. 41, 2544\u20132555 (2011).","journal-title":"Eur. J. Immunol."},{"key":"BFncomms8086_CR6","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1084\/jem.20102327","volume":"208","author":"Y Lei","year":"2011","unstructured":"Lei, Y. et al. Aire-dependent production of XCL1 mediates medullary accumulation of thymic dendritic cells and contributes to regulatory T cell development. J. Exp. Med. 208, 383\u2013394 (2011).","journal-title":"J. Exp. Med."},{"key":"BFncomms8086_CR7","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1084\/jem.20082394","volume":"206","author":"C Ohnmacht","year":"2009","unstructured":"Ohnmacht, C. et al. Constitutive ablation of dendritic cells breaks self-tolerance of CD4 T cells and results in spontaneous fatal autoimmunity. J. Exp. Med. 206, 549\u2013559 (2009).","journal-title":"J. Exp. Med."},{"key":"BFncomms8086_CR8","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1016\/j.immuni.2008.10.012","volume":"29","author":"T Birnberg","year":"2008","unstructured":"Birnberg, T. et al. Lack of conventional dendritic cells is compatible with normal development and T cell homeostasis, but causes myeloid proliferative syndrome. Immunity 29, 986\u2013997 (2008).","journal-title":"Immunity"},{"key":"BFncomms8086_CR9","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1084\/jem.20112061","volume":"210","author":"JM Coquet","year":"2013","unstructured":"Coquet, J. M. et al. Epithelial and dendritic cells in the thymic medulla promote CD4+Foxp3+ regulatory T cell development via the CD27-CD70 pathway. J. Exp. Med. 210, 715\u2013728 (2013).","journal-title":"J. Exp. Med."},{"key":"BFncomms8086_CR10","doi-asserted-by":"publisher","first-page":"6923","DOI":"10.4049\/jimmunol.181.10.6923","volume":"181","author":"S Yamazaki","year":"2008","unstructured":"Yamazaki, S. et al. CD8+ CD205+ splenic dendritic cells are specialized to induce Foxp3+ regulatory T cells. J. Immunol. 181, 6923\u20136933 (2008).","journal-title":"J. Immunol."},{"key":"BFncomms8086_CR11","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1038\/ni1428","volume":"8","author":"JM Kim","year":"2007","unstructured":"Kim, J. M., Rasmussen, J. P. & Rudensky, A. Y. Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice. Nat. Immunol. 8, 191\u2013197 (2007).","journal-title":"Nat. Immunol."},{"key":"BFncomms8086_CR12","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1136\/jmg.39.8.537","volume":"39","author":"RS Wildin","year":"2002","unstructured":"Wildin, R. S., Smyk-Pearson, S. & Filipovich, A. H. Clinical and molecular features of the immunodysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) syndrome. J. Med. Genet. 39, 537\u2013545 (2002).","journal-title":"J. Med. Genet."},{"key":"BFncomms8086_CR13","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1002\/eji.201041169","volume":"41","author":"L Bar-On","year":"2011","unstructured":"Bar-On, L., Birnberg, T., Kim, K. W. & Jung, S. Dendritic cell-restricted CD80\/86 deficiency results in peripheral regulatory T-cell reduction but is not associated with lymphocyte hyperactivation. Eur. J. Immunol. 41, 291\u2013298 (2011).","journal-title":"Eur. J. Immunol."},{"key":"BFncomms8086_CR14","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1038\/nature12873","volume":"506","author":"Y Okada","year":"2014","unstructured":"Okada, Y. et al. Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature 506, 376\u2013381 (2014).","journal-title":"Nature"},{"key":"BFncomms8086_CR15","doi-asserted-by":"crossref","first-page":"5303","DOI":"10.4049\/jimmunol.163.10.5303","volume":"163","author":"D Ashany","year":"1999","unstructured":"Ashany, D., Savir, A., Bhardwaj, N. & Elkon, K. B. Dendritic cells are resistant to apoptosis through the Fas (CD95\/APO-1) pathway. J. Immunol. 163, 5303\u20135311 (1999).","journal-title":"J. Immunol."},{"key":"BFncomms8086_CR16","doi-asserted-by":"crossref","first-page":"3478","DOI":"10.1182\/blood.V95.11.3478","volume":"95","author":"F Willems","year":"2000","unstructured":"Willems, F. et al. Expression of c-FLIP(L) and resistance to CD95-mediated apoptosis of monocyte-derived dendritic cells: inhibition by bisindolylmaleimide. Blood 95, 3478\u20133482 (2000).","journal-title":"Blood"},{"key":"BFncomms8086_CR17","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1016\/j.immuni.2007.03.016","volume":"26","author":"PB Stranges","year":"2007","unstructured":"Stranges, P. B. et al. Elimination of antigen-presenting cells and autoreactive T cells by Fas contributes to prevention of autoimmunity. Immunity 26, 629\u2013641 (2007).","journal-title":"Immunity"},{"key":"BFncomms8086_CR18","doi-asserted-by":"publisher","first-page":"6762","DOI":"10.4049\/jimmunol.165.12.6762","volume":"165","author":"AT Kamath","year":"2000","unstructured":"Kamath, A. T. et al. The development, maturation, and turnover rate of mouse spleen dendritic cell populations. J. Immunol. 165, 6762\u20136770 (2000).","journal-title":"J. Immunol."},{"key":"BFncomms8086_CR19","doi-asserted-by":"publisher","first-page":"4968","DOI":"10.1182\/blood-2009-11-252841","volume":"116","author":"QQ Huang","year":"2010","unstructured":"Huang, Q. Q. et al. FLIP: a novel regulator of macrophage differentiation and granulocyte homeostasis. Blood 116, 4968\u20134977 (2010).","journal-title":"Blood"},{"key":"BFncomms8086_CR20","doi-asserted-by":"publisher","first-page":"2462","DOI":"10.1182\/blood-2010-06-286393","volume":"118","author":"FX Hubert","year":"2011","unstructured":"Hubert, F. X. et al. Aire regulates the transfer of antigen from mTECs to dendritic cells for induction of thymic tolerance. Blood 118, 2462\u20132472 (2011).","journal-title":"Blood"},{"key":"BFncomms8086_CR21","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1038\/nri853","volume":"2","author":"SC Jameson","year":"2002","unstructured":"Jameson, S. C. Maintaining the norm: T-cell homeostasis. Nat. Rev. Immunol. 2, 547\u2013556 (2002).","journal-title":"Nat. Rev. Immunol."},{"key":"BFncomms8086_CR22","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/ni.1615","volume":"9","author":"C Waskow","year":"2008","unstructured":"Waskow, C. et al. The receptor tyrosine kinase Flt3 is required for dendritic cell development in peripheral lymphoid tissues. Nat. Immunol. 9, 676\u2013683 (2008).","journal-title":"Nat. Immunol."},{"key":"BFncomms8086_CR23","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1038\/nm1697","volume":"14","author":"N Fujikado","year":"2008","unstructured":"Fujikado, N. et al. Dcir deficiency causes development of autoimmune diseases in mice due to excess expansion of dendritic cells. Nat. Med. 14, 176\u2013180 (2008).","journal-title":"Nat. Med."},{"key":"BFncomms8086_CR24","doi-asserted-by":"publisher","first-page":"1184","DOI":"10.1038\/ni.2135","volume":"12","author":"GE Hammer","year":"2011","unstructured":"Hammer, G. E. et al. Expression of A20 by dendritic cells preserves immune homeostasis and prevents colitis and spondyloarthritis. Nat. Immunol. 12, 1184\u20131193 (2011).","journal-title":"Nat. Immunol."},{"key":"BFncomms8086_CR25","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.immuni.2011.05.013","volume":"35","author":"M Kool","year":"2011","unstructured":"Kool, M. et al. The ubiquitin-editing protein A20 prevents dendritic cell activation, recognition of apoptotic cells, and systemic autoimmunity. Immunity 35, 82\u201396 (2011).","journal-title":"Immunity"},{"key":"BFncomms8086_CR26","doi-asserted-by":"publisher","first-page":"E3311","DOI":"10.1073\/pnas.1300617110","volume":"110","author":"C Lamagna","year":"2013","unstructured":"Lamagna, C., Scapini, P., van Ziffle, J. A., DeFranco, A. L. & Lowell, C. A. Hyperactivated MyD88 signaling in dendritic cells, through specific deletion of Lyn kinase, causes severe autoimmunity and inflammation. Proc. Natl Acad. Sci. USA 110, E3311\u2013E3320 (2013).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms8086_CR27","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1084\/jem.20091627","volume":"207","author":"BT Edelson","year":"2010","unstructured":"Edelson, B. T. et al. Peripheral CD103+ dendritic cells form a unified subset developmentally related to CD8alpha+ conventional dendritic cells. J. Exp. Med. 207, 823\u2013836 (2010).","journal-title":"J. Exp. Med."},{"key":"BFncomms8086_CR28","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1126\/science.1164206","volume":"322","author":"K Hildner","year":"2008","unstructured":"Hildner, K. et al. Batf3 deficiency reveals a critical role for CD8alpha+ dendritic cells in cytotoxic T cell immunity. Science 322, 1097\u20131100 (2008).","journal-title":"Science"},{"key":"BFncomms8086_CR29","doi-asserted-by":"publisher","first-page":"11288","DOI":"10.1073\/pnas.1202208109","volume":"109","author":"T Fukaya","year":"2012","unstructured":"Fukaya, T. et al. Conditional ablation of CD205+ conventional dendritic cells impacts the regulation of T-cell immunity and homeostasis in vivo. Proc. Natl Acad. Sci. USA 109, 11288\u201311293 (2012).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms8086_CR30","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1016\/j.immuni.2008.02.018","volume":"28","author":"N Luckashenak","year":"2008","unstructured":"Luckashenak, N. et al. Constitutive crosspresentation of tissue antigens by dendritic cells controls CD8+ T cell tolerance in vivo. Immunity 28, 521\u2013532 (2008).","journal-title":"Immunity"},{"key":"BFncomms8086_CR31","doi-asserted-by":"publisher","first-page":"942148","DOI":"10.1155\/2014\/942148","volume":"2014","author":"A Hanyecz","year":"2014","unstructured":"Hanyecz, A. et al. Proteoglycan aggrecan conducting T cell activation and apoptosis in a murine model of rheumatoid arthritis. Biomed. Res. Int. 2014, 942148 (2014).","journal-title":"Biomed. Res. Int."},{"key":"BFncomms8086_CR32","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1136\/ard.2008.103978","volume":"69","author":"H de Jong","year":"2010","unstructured":"de Jong, H. et al. Cartilage proteoglycan aggrecan epitopes induce proinflammatory autoreactive T-cell responses in rheumatoid arthritis and osteoarthritis. Ann. Rheum. Dis. 69, 255\u2013262 (2010).","journal-title":"Ann. Rheum. Dis."},{"key":"BFncomms8086_CR33","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1002\/art.24293","volume":"60","author":"LG Alexopoulos","year":"2009","unstructured":"Alexopoulos, L. G., Youn, I., Bonaldo, P. & Guilak, F. Developmental and osteoarthritic changes in Col6a1-knockout mice: biomechanics of type VI collagen in the cartilage pericellular matrix. Arthritis Rheum. 60, 771\u2013779 (2009).","journal-title":"Arthritis Rheum."},{"key":"BFncomms8086_CR34","doi-asserted-by":"publisher","first-page":"R154","DOI":"10.1186\/ar2831","volume":"11","author":"JJ Manson","year":"2009","unstructured":"Manson, J. J. et al. Relationship between anti-dsDNA, anti-nucleosome and anti-alpha-actinin antibodies and markers of renal disease in patients with lupus nephritis: a prospective longitudinal study. Arthritis Res. Ther. 11, R154 (2009).","journal-title":"Arthritis Res. Ther."},{"key":"BFncomms8086_CR35","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1007\/s10875-006-9045-z","volume":"26","author":"P Gueguen","year":"2006","unstructured":"Gueguen, P. et al. Double reactivity against actin and alpha-actinin defines a severe form of autoimmune hepatitis type 1. J. Clin. Immunol. 26, 495\u2013505 (2006).","journal-title":"J. Clin. Immunol."},{"key":"BFncomms8086_CR36","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1038\/nri3254","volume":"12","author":"OP Joffre","year":"2012","unstructured":"Joffre, O. P., Segura, E., Savina, A. & Amigorena, S. Cross-presentation by dendritic cells. Nat. Rev. Immunol. 12, 557\u2013569 (2012).","journal-title":"Nat. Rev. Immunol."},{"key":"BFncomms8086_CR37","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1016\/j.it.2012.04.009","volume":"33","author":"C Dresch","year":"2012","unstructured":"Dresch, C., Leverrier, Y., Marvel, J. & Shortman, K. Development of antigen cross-presentation capacity in dendritic cells. Trends Immunol. 33, 381\u2013388 (2012).","journal-title":"Trends Immunol."},{"key":"BFncomms8086_CR38","doi-asserted-by":"publisher","first-page":"6494","DOI":"10.1073\/pnas.1221955110","volume":"110","author":"RS Paiva","year":"2013","unstructured":"Paiva, R. S. et al. Recent thymic emigrants are the preferential precursors of regulatory T cells differentiated in the periphery. Proc. Natl Acad. Sci. USA 110, 6494\u20136499 (2013).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms8086_CR39","first-page":"844","volume":"123","author":"J Idoyaga","year":"2013","unstructured":"Idoyaga, J. et al. Specialized role of migratory dendritic cells in peripheral tolerance induction. J. Clin. Invest. 123, 844\u2013854 (2013).","journal-title":"J. Clin. Invest."},{"key":"BFncomms8086_CR40","doi-asserted-by":"publisher","first-page":"1897","DOI":"10.1182\/blood-2009-08-237784","volume":"115","author":"DA Zlotoff","year":"2010","unstructured":"Zlotoff, D. A. et al. CCR7 and CCR9 together recruit hematopoietic progenitors to the adult thymus. Blood 115, 1897\u20131905 (2010).","journal-title":"Blood"},{"key":"BFncomms8086_CR41","first-page":"87","volume":"373","author":"SL Zhang","year":"2014","unstructured":"Zhang, S. L. & Bhandoola, A. Trafficking to the thymus. Curr. Top. Microbiol. Immunol. 373, 87\u2013111 (2014).","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"BFncomms8086_CR42","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1084\/jem.20062259","volume":"204","author":"K Hirota","year":"2007","unstructured":"Hirota, K. et al. T cell self-reactivity forms a cytokine milieu for spontaneous development of IL-17+ Th cells that cause autoimmune arthritis. J. Exp. Med. 204, 41\u201347 (2007).","journal-title":"J. Exp. Med."},{"key":"BFncomms8086_CR43","doi-asserted-by":"publisher","first-page":"4171","DOI":"10.4049\/jimmunol.1103598","volume":"188","author":"S Oh","year":"2012","unstructured":"Oh, S. et al. Requirement for diverse TCR specificities determines regulatory T cell activity in a mouse model of autoimmune arthritis. J. Immunol. 188, 4171\u20134180 (2012).","journal-title":"J. Immunol."},{"key":"BFncomms8086_CR44","doi-asserted-by":"publisher","first-page":"170","DOI":"10.4049\/jimmunol.1101311","volume":"188","author":"RJ Martinez","year":"2012","unstructured":"Martinez, R. J. et al. Arthritogenic self-reactive CD4+ T cells acquire an FR4hiCD73hi anergic state in the presence of Foxp3+ regulatory T cells. J. Immunol. 188, 170\u2013181 (2012).","journal-title":"J. Immunol."},{"key":"BFncomms8086_CR45","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1002\/art.21567","volume":"54","author":"E Jang","year":"2006","unstructured":"Jang, E. et al. Prevention of spontaneous arthritis by inhibiting homeostatic expansion of autoreactive CD4+ T cells in the K\/BxN mouse model. Arthritis Rheum. 54, 492\u2013498 (2006).","journal-title":"Arthritis Rheum."},{"key":"BFncomms8086_CR46","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1177\/014107688908200806","volume":"82","author":"DP Symmons","year":"1989","unstructured":"Symmons, D. P., Farr, M., Salmon, M. & Bacon, P. A. Lymphopenia in rheumatoid arthritis. J. R. Soc. Med. 82, 462\u2013463 (1989).","journal-title":"J. R. Soc. Med."},{"key":"BFncomms8086_CR47","doi-asserted-by":"publisher","first-page":"4550","DOI":"10.1182\/blood-2002-03-0671","volume":"100","author":"F Ponchel","year":"2002","unstructured":"Ponchel, F. et al. Dysregulated lymphocyte proliferation and differentiation in patients with rheumatoid arthritis. Blood 100, 4550\u20134556 (2002).","journal-title":"Blood"},{"key":"BFncomms8086_CR48","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1038\/ni.1818","volume":"11","author":"K Wing","year":"2010","unstructured":"Wing, K. & Sakaguchi, S. Regulatory T cells exert checks and balances on self tolerance and autoimmunity. Nat. Immunol. 11, 7\u201313 (2010).","journal-title":"Nat. Immunol."},{"key":"BFncomms8086_CR49","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1136\/ard.2007.086066","volume":"68","author":"H Kelchtermans","year":"2009","unstructured":"Kelchtermans, H. et al. Activated CD4+CD25+ regulatory T cells inhibit osteoclastogenesis and collagen-induced arthritis. Ann. Rheum. Dis. 68, 744\u2013750 (2009).","journal-title":"Ann. Rheum. Dis."},{"key":"BFncomms8086_CR50","doi-asserted-by":"publisher","first-page":"7238","DOI":"10.4049\/jimmunol.0903841","volume":"184","author":"MM Zaiss","year":"2010","unstructured":"Zaiss, M. M. et al. Regulatory T cells protect from local and systemic bone destruction in arthritis. J. Immunol. 184, 7238\u20137246 (2010).","journal-title":"J. Immunol."},{"key":"BFncomms8086_CR51","doi-asserted-by":"publisher","first-page":"1546","DOI":"10.4049\/jimmunol.1002942","volume":"186","author":"E Jang","year":"2011","unstructured":"Jang, E. et al. Foxp3+ regulatory T cells control humoral autoimmunity by suppressing the development of long-lived plasma cells. J. Immunol. 186, 1546\u20131553 (2011).","journal-title":"J. Immunol."},{"key":"BFncomms8086_CR52","doi-asserted-by":"publisher","first-page":"1911","DOI":"10.1084\/jem.20070285","volume":"204","author":"HJ Wu","year":"2007","unstructured":"Wu, H. J. et al. Inflammatory arthritis can be reined in by CpG-induced DC-NK cell cross talk. J. Exp. Med. 204, 1911\u20131922 (2007).","journal-title":"J. Exp. Med."},{"key":"BFncomms8086_CR53","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1084\/jem.20061531","volume":"204","author":"S Nadkarni","year":"2007","unstructured":"Nadkarni, S., Mauri, C. & Ehrenstein, M. R. Anti-TNF-alpha therapy induces a distinct regulatory T cell population in patients with rheumatoid arthritis via TGF-beta. J. Exp. Med. 204, 33\u201339 (2007).","journal-title":"J. Exp. Med."},{"key":"BFncomms8086_CR54","doi-asserted-by":"publisher","first-page":"2517","DOI":"10.3899\/jrheum.110283","volume":"38","author":"SY Kawashiri","year":"2011","unstructured":"Kawashiri, S. Y. et al. CD4+CD25(high)CD127(low\/-) Treg cell frequency from peripheral blood correlates with disease activity in patients with rheumatoid arthritis. J. Rheumatol. 38, 2517\u20132521 (2011).","journal-title":"J. Rheumatol."},{"key":"BFncomms8086_CR55","doi-asserted-by":"crossref","first-page":"2567","DOI":"10.1002\/art.38058","volume":"65","author":"U Wagner","year":"2013","unstructured":"Wagner, U., Schatz, A., Baerwald, C. & Rossol, M. Brief report: deficient thymic output in rheumatoid arthritis despite abundance of prethymic progenitors. Arthritis Rheum. 65, 2567\u20132572 (2013).","journal-title":"Arthritis Rheum."},{"key":"BFncomms8086_CR56","doi-asserted-by":"publisher","first-page":"e3633","DOI":"10.1371\/journal.pone.0003633","volume":"3","author":"M Dehlin","year":"2008","unstructured":"Dehlin, M. et al. Intra-articular fms-like tyrosine kinase 3 ligand expression is a driving force in induction and progression of arthritis. PLoS ONE 3, e3633 (2008).","journal-title":"PLoS ONE"},{"key":"BFncomms8086_CR57","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1002\/art.11487","volume":"50","author":"J Zwerina","year":"2004","unstructured":"Zwerina, J. et al. Single and combined inhibition of tumor necrosis factor, interleukin-1, and RANKL pathways in tumor necrosis factor-induced arthritis: effects on synovial inflammation, bone erosion, and cartilage destruction. Arthritis Rheum. 50, 277\u2013290 (2004).","journal-title":"Arthritis Rheum."},{"key":"BFncomms8086_CR58","doi-asserted-by":"publisher","first-page":"3638","DOI":"10.1002\/art.34610","volume":"64","author":"QQ Huang","year":"2012","unstructured":"Huang, Q. Q. et al. Gp96 prpetuates the persistent inflammation of rheumatoid arthritis. Arthritis Rheum. 64, 3638\u20133648 (2012).","journal-title":"Arthritis Rheum."},{"key":"BFncomms8086_CR59","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1002\/art.38198","volume":"66","author":"QQ Huang","year":"2014","unstructured":"Huang, Q. Q. et al. Fas signaling in macrophages promotes chronicity in K\/BxN serum-induced arthritis. Arthritis Rheumatol. 66, 68\u201377 (2014).","journal-title":"Arthritis Rheumatol."},{"key":"BFncomms8086_CR60","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1189\/jlb.0912473","volume":"93","author":"QQ Huang","year":"2013","unstructured":"Huang, Q. Q. et al. TLR2 deletion promotes arthritis through reduction of IL-10. J. Leukoc. Biol. 93, 751\u2013759 (2013).","journal-title":"J. Leukoc. Biol."},{"key":"BFncomms8086_CR61","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1111\/j.0300-9475.2005.01548.x","volume":"61","author":"JD Mountz","year":"2005","unstructured":"Mountz, J. D. et al. Genetic segregation of spontaneous erosive arthritis and generalized autoimmune disease in the BXD2 recombinant inbred strain of mice. Scand. J. Immunol. 61, 128\u2013138 (2005).","journal-title":"Scand. J. Immunol."},{"key":"BFncomms8086_CR62","doi-asserted-by":"publisher","first-page":"1791","DOI":"10.1172\/JCI60975","volume":"122","author":"U Harre","year":"2012","unstructured":"Harre, U. et al. Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin. J. Clin. Invest. 122, 1791\u20131802 (2012).","journal-title":"J. Clin. Invest."},{"key":"BFncomms8086_CR63","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1038\/nbt859","volume":"21","author":"WH Robinson","year":"2003","unstructured":"Robinson, W. H. et al. Protein microarrays guide tolerizing DNA vaccine treatment of autoimmune encephalomyelitis. Nat. Biotechnol. 21, 1033\u20131039 (2003).","journal-title":"Nat. Biotechnol."},{"key":"BFncomms8086_CR64","doi-asserted-by":"publisher","first-page":"5184","DOI":"10.4049\/jimmunol.1002683","volume":"186","author":"P Sathe","year":"2011","unstructured":"Sathe, P. et al. The acquisition of antigen cross-presentation function by newly formed dendritic cells. J. Immunol. 186, 5184\u20135192 (2011).","journal-title":"J. Immunol."},{"key":"BFncomms8086_CR65","doi-asserted-by":"publisher","first-page":"2049","DOI":"10.1038\/nprot.2007.296","volume":"2","author":"BJ Quah","year":"2007","unstructured":"Quah, B. J., Warren, H. S. & Parish, C. R. Monitoring lymphocyte proliferation in vitro and in vivo with the intracellular fluorescent dye carboxyfluorescein diacetate succinimidyl ester. Nat. Protoc. 2, 2049\u20132056 (2007).","journal-title":"Nat. Protoc."}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/ncomms8086.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/ncomms8086","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/ncomms8086.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T06:35:58Z","timestamp":1672900558000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/ncomms8086"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,5,12]]},"references-count":65,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2015,11,3]]}},"alternative-id":["BFncomms8086"],"URL":"https:\/\/doi.org\/10.1038\/ncomms8086","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.725486816.793507198","asserted-by":"object"}]},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,5,12]]},"assertion":[{"value":"4 February 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 April 2015","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 May 2015","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"7086"}}