{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T22:08:50Z","timestamp":1791497330346,"version":"4.3.4"},"reference-count":71,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T00:00:00Z","timestamp":1672876800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["P30 AR070253, R01 AR075906, R01 AR073201, K08 AR072791, R01 AR078769, K08 AR073339"],"award-info":[{"award-number":["P30 AR070253, R01 AR075906, R01 AR073201, K08 AR072791, R01 AR078769, K08 AR073339"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000861","name":"Burroughs Wellcome Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000861","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001680","name":"Charles H. Hood Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001680","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006260","name":"Rheumatology Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006260","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000964","name":"Arthritis National Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000964","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>T peripheral helper (Tph) cells, identified in the synovium of adults with seropositive rheumatoid arthritis, drive B cell maturation and antibody production in non-lymphoid tissues. We sought to determine if similarly dysregulated T cell-B cell interactions underlie another form of inflammatory arthritis, juvenile oligoarthritis (oligo JIA). Clonally expanded Tph cells able to promote B cell antibody production preferentially accumulated in the synovial fluid (SF) of oligo JIA patients with antinuclear antibodies (ANA) compared to autoantibody-negative patients. Single-cell transcriptomics enabled further definition of the Tph gene signature in inflamed tissues and showed that Tph cells from ANA-positive patients upregulated genes associated with B cell help to a greater extent than patients without autoantibodies. T cells that co-expressed regulatory T and B cell-help factors were identified. The phenotype of these Tph-like Treg cells suggests an ability to restrain T cell-B cell interactions in tissues. Our findings support the central role of disordered T cell-help to B cells in autoantibody-positive arthritides.<\/jats:p>","DOI":"10.3389\/fimmu.2022.1068399","type":"journal-article","created":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T09:29:05Z","timestamp":1672910945000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Disordered T cell-B cell interactions in autoantibody-positive inflammatory arthritis"],"prefix":"10.3389","volume":"13","author":[{"given":"Am\u00e9lie M.","family":"Jul\u00e9","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ki Pui","family":"Lam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kacie J.","family":"Hoyt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Gutierrez-Arcelus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siobhan M.","family":"Case","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mia","family":"Chandler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret H.","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ezra M.","family":"Cohen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatma","family":"Dedeoglu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olha","family":"Halyabar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Hausmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa M.","family":"Hazen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"Janssen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Lo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mindy S.","family":"Lo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esra","family":"Meidan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan E.","family":"Roberts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly","family":"Wobma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Beth F.","family":"Son","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert P.","family":"Sundel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pui Y.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter T.","family":"Sage","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Talal A.","family":"Chatila","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A.","family":"Nigrovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak A.","family":"Rao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren A.","family":"Henderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.11.1545","article-title":"Follicular b helper T cells express CXC chemokine receptor 5, localize to b cell follicles, and support immunoglobulin production","volume":"192","author":"Breitfeld","year":"2000","journal-title":"J Exp Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.11.1553","article-title":"CXC chemokine receptor 5 expression defines follicular homing T cells with b cell helper function","volume":"192","author":"Schaerli","year":"2000","journal-title":"J Exp Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1038\/35876","article-title":"A b-cell-homing chemokine made in lymphoid follicles activates burkitt's lymphoma receptor-1","volume":"391","author":"Gunn","year":"1998","journal-title":"Nature"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.07.002","article-title":"The transcriptional repressor bcl-6 directs T follicular helper cell lineage commitment","volume":"31","author":"Yu","year":"2009","journal-title":"Immunity"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1126\/science.1175870","article-title":"Bcl6 and blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation","volume":"325","author":"Johnston","year":"2009","journal-title":"Science"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-0706-5","article-title":"Bcl-6 is the nexus transcription factor of T follicular helper cells via repressor-of-repressor circuits","volume":"21","author":"Choi","year":"2020","journal-title":"Nat Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20141380","article-title":"BCL6 orchestrates tfh cell differentiation via multiple distinct mechanisms","volume":"212","author":"Hatzi","year":"2015","journal-title":"J Exp Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20091777","article-title":"IL-21 regulates germinal center b cell differentiation and proliferation through a b cell-intrinsic mechanism","volume":"207","author":"Zotos","year":"2010","journal-title":"J Exp Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/nature20810","article-title":"Pathologically expanded peripheral T helper cell subset drives b cells in rheumatoid arthritis","volume":"542","author":"Rao","year":"2017","journal-title":"Nature"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/nature12058","article-title":"Follicular T-helper cell recruitment governed by bystander b cells and ICOS-driven motility","volume":"496","author":"Xu","year":"2013","journal-title":"Nature"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1103246","article-title":"Bcl6 and maf cooperate to instruct human follicular helper CD4 T cell differentiation","volume":"188","author":"Kroenke","year":"2012","journal-title":"J Immunol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"68","DOI":"10.4049\/jimmunol.173.1.68","article-title":"T Follicular helper cells express a distinctive transcriptional profile, reflecting their role as non-Th1\/Th2 effector cells that provide help for b cells","volume":"173","author":"Chtanova","year":"2004","journal-title":"J Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.06.001","article-title":"A fundamental role for interleukin-21 in the generation of T follicular helper cells","volume":"29","author":"Vogelzang","year":"2008","journal-title":"Immunity"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1877","article-title":"PD-1 regulates germinal center b cell survival and the formation and affinity of long-lived plasma cells","volume":"11","author":"Good-Jacobson","year":"2010","journal-title":"Nat Immunol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/35051107","article-title":"ICOS is critical for CD40-mediated antibody class switching","volume":"409","author":"McAdam","year":"2001","journal-title":"Nature"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.03.023","article-title":"ICOS receptor instructs T follicular helper cell versus effector cell differentiation via induction of the transcriptional repressor Bcl6","volume":"34","author":"Choi","year":"2011","journal-title":"Immunity"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2426","article-title":"Follicular regulatory T cells expressing Foxp3 and bcl-6 suppress germinal center reactions","volume":"17","author":"Chung","year":"2011","journal-title":"Nat Med"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2425","article-title":"Foxp3+ follicular regulatory T cells control the germinal center response","volume":"17","author":"Linterman","year":"2011","journal-title":"Nat Med"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1101328","article-title":"Regulation of the germinal center reaction by Foxp3+ follicular regulatory T cells","volume":"187","author":"Wollenberg","year":"2011","journal-title":"J Immunol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3578","article-title":"Suppression by TFR cells leads to durable and selective inhibition of b cell effector function","volume":"17","author":"Sage","year":"2016","journal-title":"Nat Immunol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20170901","article-title":"Deficiency in T follicular regulatory cells promotes autoimmunity","volume":"215","author":"Fu","year":"2018","journal-title":"J Exp Med"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0472-4","article-title":"Follicular regulatory T cells control humoral and allergic immunity by restraining early b cell responses","volume":"20","author":"Clement","year":"2019","journal-title":"Nat Immunol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kel225","article-title":"Lymphoid neogenesis in juvenile idiopathic arthritis correlates with ANA positivity and plasma cells infiltration","volume":"46","author":"Gregorio","year":"2007","journal-title":"Rheumatology"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.2.1072","article-title":"Lymphoid neogenesis in rheumatoid synovitis","volume":"167","author":"Takemura","year":"2001","journal-title":"J Immunol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1002\/art.27767","article-title":"V-Region gene analysis of locally defined synovial b and plasma cells reveals selected b cell expansion and accumulation of plasma cell clones in rheumatoid arthritis","volume":"63","author":"Scheel","year":"2011","journal-title":"Arthritis Rheumatism"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1002\/art.20945","article-title":"Patients with antinuclear antibody-positive juvenile idiopathic arthritis constitute a homogeneous subgroup irrespective of the course of joint disease","volume":"52","author":"Ravelli","year":"2005","journal-title":"Arthritis Rheumatism"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1002\/art.30076","article-title":"Antinuclear antibody-positive patients should be grouped as a separate category in the classification of juvenile idiopathic arthritis","volume":"63","author":"Ravelli","year":"2011","journal-title":"Arthritis Rheumatism"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1002\/art.22381","article-title":"Prevalence, risk factors, and outcome of uveitis in juvenile idiopathic arthritis: a long-term followup study","volume":"56","author":"Saurenmann","year":"2007","journal-title":"Arthritis Rheumatism"},{"key":"B29","article-title":"International league of associations for rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001","volume":"31","author":"Petty","year":"2004","journal-title":"J Rheumatol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1002\/art.40410","article-title":"Switched memory b cells are increased in oligoarticular and polyarticular juvenile idiopathic arthritis and their change over time is related to response to tumor necrosis factor inhibitors","volume":"70","author":"Marasco","year":"2018","journal-title":"Arthritis Rheumatol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1002\/art.27657","article-title":"Biologic similarities based on age at onset in oligoarticular and polyarticular subtypes of juvenile idiopathic arthritis","volume":"62","author":"Barnes","year":"2010","journal-title":"Arthritis Rheumatism"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1002\/art.27424","article-title":"Juvenile idiopathic arthritis and HLA class I and class II interactions and age-at-onset effects","volume":"62","author":"Hollenbach","year":"2010","journal-title":"Arthritis Rheumatism"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199909)42:9<1843::AID-ANR8>3.0.CO;2-M","article-title":"Age-specific effects of juvenile rheumatoid arthritis-associated HLA alleles","volume":"42","author":"Murray","year":"1999","journal-title":"Arthritis Rheumatism"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.149185","article-title":"Th1 polarization defines the synovial fluid T cell compartment in oligoarticular juvenile idiopathic arthritis","volume":"6","author":"Jule","year":"2021","journal-title":"JCI Insight"},{"key":"B35","doi-asserted-by":"publisher","first-page":"108484","DOI":"10.1016\/j.clim.2020.108484","article-title":"IL-21(+) CD4(+) T helper cells co-expressing IFN-gamma and TNF-alpha accumulate in the joints of antinuclear antibody positive patients with juvenile idiopathic arthritis","volume":"217","author":"Fischer","year":"2020","journal-title":"Clin Immunol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.130062","article-title":"PD-1hiCXCR5- T peripheral helper cells promote b cell responses in lupus via MAF and IL-21","volume":"4","author":"Bocharnikov","year":"2019","journal-title":"JCI Insight"},{"key":"B37","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1111\/imr.12747","article-title":"TFH cells in bystander and cognate interactions with b cells","volume":"288","author":"Wan","year":"2019","journal-title":"Immunol Rev"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1084\/jem.187.4.655","article-title":"B cell-attracting chemokine 1, a human CXC chemokine expressed in lymphoid tissues, selectively attracts b lymphocytes via BLR1\/CXCR5","volume":"187","author":"Legler","year":"1998","journal-title":"J Exp Med"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.12.7867","article-title":"IL-21 induces differentiation of human naive and memory b cells into antibody-secreting plasma cells","volume":"175","author":"Ettinger","year":"2005","journal-title":"J Immunol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.9.5154","article-title":"Cutting edge: IL-21 is a switch factor for the production of IgG1 and IgG3 by human b cells","volume":"172","author":"Pene","year":"2004","journal-title":"J Immunol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1002\/art.41913","article-title":"Effect of Clonally Expanded PD-1high CXCR5-CD4+ Peripheral T Helper Cells on B Cell Differentiation in the Joints of Patients With Antinuclear Antibody-Positive Juvenile Idiopathic Arthritis","volume":"74","author":"Fischer","year":"2022","journal-title":"Arthritis Rheumatol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-09-243071","article-title":"Complement receptor 2\/CD21- human naive b cells contain mostly autoreactive unresponsive clones","volume":"115","author":"Isnardi","year":"2010","journal-title":"Blood"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0901984106","article-title":"Circulating CD21low b cells in common variable immunodeficiency resemble tissue homing, innate-like b cells","volume":"106","author":"Rakhmanov","year":"2009","journal-title":"Proc Natl Acad Sci United States America"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20181134","article-title":"FoxP3 and Ezh2 regulate tfr cell suppressive function and transcriptional program","volume":"216","author":"Hou","year":"2019","journal-title":"J Exp Med"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202048797","article-title":"Antigen-driven PD-1(+) TOX(+) BHLHE40(+) and PD-1(+) TOX(+) EOMES(+) T lymphocytes regulate juvenile idiopathic arthritis in situ","volume":"51","author":"Maschmeyer","year":"2021","journal-title":"Eur J Immunol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20091548","article-title":"Batf coordinates multiple aspects of b and T cell function required for normal antibody responses","volume":"207","author":"Betz","year":"2010","journal-title":"J Exp Med"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0378-1","article-title":"Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry","volume":"20","author":"Zhang","year":"2019","journal-title":"Nat Immunol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1705551114","article-title":"A distinct subpopulation of CD25(-) T-follicular regulatory cells localizes in the germinal centers","volume":"114","author":"Wing","year":"2017","journal-title":"Proc Natl Acad Sci United States America"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0403-9","article-title":"Distinct phenotype of CD4(+) T cells driving celiac disease identified in multiple autoimmune conditions","volume":"25","author":"Christophersen","year":"2019","journal-title":"Nat Med"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2018-214885","article-title":"Multi-dimensional analysis identified rheumatoid arthritis-driving pathway in human T cell","volume":"78","author":"Takeshita","year":"2019","journal-title":"Ann Rheumatic Dis"},{"key":"B51","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1186\/s13075-020-02349-y","article-title":"T Helper cells in synovial fluid of patients with rheumatoid arthritis primarily have a Th1 and a CXCR3(+)Th2 phenotype","volume":"22","author":"Aldridge","year":"2020","journal-title":"Arthritis Res Ther"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2000783","article-title":"Autoreactivity of peripheral helper T cells in the joints of rheumatoid arthritis","volume":"206","author":"Sakuragi","year":"2021","journal-title":"J Immunol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1002\/art.38735","article-title":"Interleukin-21 promotes germinal center reaction by skewing the follicular regulatory T cell to follicular helper T cell balance in autoimmune BXD2 mice","volume":"66","author":"Ding","year":"2014","journal-title":"Arthritis Rheumatol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201546043","article-title":"TGF-beta induces the differentiation of human CXCL13-producing CD4(+) T cells","volume":"46","author":"Kobayashi","year":"2016","journal-title":"Eur J Immunol"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201546094","article-title":"Follicular regulatory T cells repress cytokine production by follicular helper T cells and optimize IgG responses in mice","volume":"46","author":"Wu","year":"2016","journal-title":"Eur J Immunol"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20130604","article-title":"Follicular regulatory T cells control humoral autoimmunity via NFAT2-regulated CXCR5 expression","volume":"211","author":"Vaeth","year":"2014","journal-title":"J Exp Med"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2020.09.002","article-title":"Transcription factor Bhlhe40 in immunity and autoimmunity","volume":"41","author":"Cook","year":"2020","journal-title":"Trends Immunol"},{"key":"B58","doi-asserted-by":"publisher","first-page":"3551","DOI":"10.1038\/ncomms4551","article-title":"Bhlhe40 controls cytokine production by T cells and is essential for pathogenicity in autoimmune neuroinflammation","volume":"5","author":"Lin","year":"2014","journal-title":"Nat Commun"},{"key":"B59","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1016\/j.immuni.2019.08.013","article-title":"The transcription factor Bhlhe40 programs mitochondrial regulation of resident CD8(+) T cell fitness and functionality","volume":"51","author":"Li","year":"2019","journal-title":"Immunity"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1038\/nature24993","article-title":"Runx3 programs CD8(+) T cell residency in non-lymphoid tissues and tumours","volume":"552","author":"Milner","year":"2017","journal-title":"Nature"},{"key":"B61","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1101\/gad.320663.118","article-title":"Helix-loop-helix proteins and the advent of cellular diversity: 30 years of discovery","volume":"33","author":"Murre","year":"2019","journal-title":"Genes Dev"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3461","article-title":"Id2 reinforces TH1 differentiation and inhibits E2A to repress TFH differentiation","volume":"17","author":"Shaw","year":"2016","journal-title":"Nat Immunol"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2928","article-title":"Id2 and Id3 maintain the regulatory T cell pool to suppress inflammatory disease","volume":"15","author":"Miyazaki","year":"2014","journal-title":"Nat Immunol"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1900358","article-title":"The transcriptional regulator Id2 is critical for adipose-resident regulatory T cell differentiation, survival, and function","volume":"203","author":"Frias","year":"2019","journal-title":"J Immunol"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1016\/S0049-0172(96)80009-6","article-title":"Epidemiology of chronic arthritis in childhood","volume":"26","author":"Oen","year":"1996","journal-title":"Semin Arthritis Rheumatism"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0619-0","article-title":"Fast, sensitive and accurate integration of single-cell data with harmony","volume":"16","author":"Korsunsky","year":"2019","journal-title":"Nat Methods"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4096","article-title":"Integrating single-cell transcriptomic data across different conditions, technologies, and species","volume":"36","author":"Butler","year":"2018","journal-title":"Nat Biotechnol"},{"key":"B68","doi-asserted-by":"publisher","first-page":"3573","DOI":"10.1016\/j.cell.2021.04.048","article-title":"Integrated analysis of multimodal single-cell data","volume":"184","author":"Hao","year":"2021","journal-title":"Cell"},{"key":"B69","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1016\/j.immuni.2007.09.010","article-title":"Foxp3 transcription-factor-dependent and -independent regulation of the regulatory T cell transcriptional signature","volume":"27","author":"Hill","year":"2007","journal-title":"Immunity"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: an r package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"Omics J Integr Biol"},{"key":"B71","article-title":"The reactome pathway knowledgebase","volume":"48","author":"Jassal","year":"2020","journal-title":"Nucleic Acids Res"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.1068399\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T09:29:13Z","timestamp":1672910953000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.1068399\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,5]]},"references-count":71,"alternative-id":["10.3389\/fimmu.2022.1068399"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.1068399","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,5]]},"article-number":"1068399"}}