{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T22:41:32Z","timestamp":1770676892458,"version":"3.49.0"},"reference-count":89,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"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>Successful induction of protective T cells by recombinant protein vaccines requires adjuvants. The liposomal adjuvant system CAF01 induces robust Th17 responses in mice. CAF01 contains the synthetic glycolipid trehalose-6,6-dibehenate (TDB), whose recognition by the C-type lectin receptor Mincle is required for Th17 induction. In previous work, we identified a pivotal role of TNF in upregulation of Mincle expression in macrophages and Th17 adjuvanticity of CAF01. The question has remained on which cell type(s) TNF acts to mediate the Th17 adjuvanticity of CAF01, and whether TNF-induced Mincle upregulation is causative. We used conditional TNFR1-deficient mice to dissect cell type-specific contributions of TNF signaling in myeloid cells, DC and T cells to Th17 induction by the recombinant tuberculosis fusion protein H1 adjuvanted with CAF01. LysM-Cre-mediated deletion of TNFR1 on myeloid cells completely abrogated vaccine-induced Th17 differentiation, replicating the phenotype in mice deficient in TNF or treated with the TNF blocker Etanercept. In contrast, TNFR1 deletion in DC by Clec9a-Cre did not affect Th17 induction, and by CD11c-Cre only partially reduced Th17 cells. T cell-specific deletion of TNFR1 by Lck-Cre had no impact on Th17 differentiation after vaccination. TNFR1 was expressed highly, and deleted efficiently via LysM-Cre, in monocytes and in neutrophils. We recently showed that neutrophils are not required for the adjuvant effect of CAF01, but monocytes are essential. Therefore, we analyzed activation of monocytes by TDB and observed robust upregulation of Mincle expression and of the Th17-inducing cytokines IL-1\u03b2 and IL-6, that was inhibited by Etanercept. Finally, we asked whether Th17 induction by TNF is causally linked to Mincle upregulation. Constitutive, TNF-independent transgenic Mincle expression partially restored Th17 induction by CAF01 despite TNF blockade. Thus, upregulation of Mincle by TNF plays a causal role, likely by enabling production of Th17-polarizing cytokines by myeloid cells upon enhanced sensing of the adjuvant component TDB.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1746618","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T05:22:48Z","timestamp":1770614568000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Mincle-dependent Th17 adjuvanticity requires TNFR1 signaling in myeloid cells"],"prefix":"10.3389","volume":"17","author":[{"given":"Robert","family":"Blamberg","sequence":"first","affiliation":[{"name":"Institute of Clinical Microbiology, Immunology and Hygiene, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg","place":["Erlangen, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carl","family":"Haberkamp","sequence":"additional","affiliation":[{"name":"Institute of Clinical Microbiology, Immunology and Hygiene, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg","place":["Erlangen, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriel Kristian","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Center for Vaccine Research, Statens Serum Institut","place":["Copenhagen, Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ida","family":"Rosenkrands","sequence":"additional","affiliation":[{"name":"Center for Vaccine Research, Statens Serum Institut","place":["Copenhagen, Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrike","family":"Schleicher","sequence":"additional","affiliation":[{"name":"Institute of Clinical Microbiology, Immunology and Hygiene, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg","place":["Erlangen, Germany"]},{"name":"FAU Profile Center Immunomedicine (FAU I-MED), Friedrich-Alexander-Universit\u00e4t (FAU), Erlangen-N\u00fcrnberg","place":["Erlangen, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara U.","family":"Schraml","sequence":"additional","affiliation":[{"name":"Biomedical Center Munich, Institute of Immunology, Faculty of Medicine, Ludwig-Maximilians-Universit\u00e4t Mu\u0308nchen","place":["Planegg-Martinsried, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sho","family":"Yamasaki","sequence":"additional","affiliation":[{"name":"Department of Molecular Immunology, Research Institute for Microbial Diseases (RIMD), Osaka University","place":["Suita, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roland","family":"Lang","sequence":"additional","affiliation":[{"name":"Institute of Clinical Microbiology, Immunology and Hygiene, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg","place":["Erlangen, Germany"]},{"name":"FAU Profile Center Immunomedicine (FAU I-MED), Friedrich-Alexander-Universit\u00e4t (FAU), Erlangen-N\u00fcrnberg","place":["Erlangen, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"48","DOI":"10.3390\/antib4010048","article-title":"Targeting sTNF\/TNFR1 signaling as a new therapeutic strategy","volume":"4","author":"Fischer","year":"2015","journal-title":"Antibodies"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00035-19","article-title":"Infectious complications of biological and small molecule targeted immunomodulatory therapies","volume":"33","author":"Davis","year":"2020","journal-title":"Clin Microbiol Rev"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-021-00694-9","article-title":"Reactivation of latent tuberculosis with TNF inhibitors: critical role of the beta 2 chain of the IL-12 receptor","volume":"18","author":"Robert","year":"2021","journal-title":"Cell Mol Immunol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kes202","article-title":"TNF blockers show distinct patterns of immune response to the pandemic influenza A H1N1 vaccine in inflammatory arthritis patients","volume":"51","author":"Fran\u00e7a","year":"2012","journal-title":"Rheumatol (Oxford)"},{"key":"B5","doi-asserted-by":"publisher","first-page":"R209","DOI":"10.1186\/ar3542","article-title":"Decreased influenza-specific B cell responses in rheumatoid arthritis patients treated with anti-tumor necrosis factor","volume":"13","author":"Kobie","year":"2011","journal-title":"Arthritis Res Ther"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.crohns.2012.05.011","article-title":"Immune response to influenza A\/H1N1 vaccine in inflammatory bowel disease patients treated with anti TNF-\u03b1 agents: effects of combined therapy with immunosuppressants","volume":"7","author":"Andrisani","year":"2013","journal-title":"J Crohns Colitis"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0b013e31827febe9","article-title":"Kinetics of anti-hepatitis B surface antigen titers after hepatitis B vaccination in patients with inflammatory bowel disease","volume":"19","author":"Gisbert","year":"2013","journal-title":"Inflammation Bowel Dis"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izx001","article-title":"Antibody response to hepatitis B virus vaccine is impaired in patients with inflammatory bowel disease on infliximab therapy","volume":"24","author":"Pratt","year":"2018","journal-title":"Inflammation Bowel Dis"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2011-201270","article-title":"Anti-TNF treatment blocks the induction of T cell-dependent humoral responses","volume":"72","author":"Salinas","year":"2013","journal-title":"Ann Rheum Dis"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.21800","article-title":"Effects of immunosuppression on immune response to pneumococcal vaccine in inflammatory bowel disease: a prospective study","volume":"18","author":"Fiorino","year":"2012","journal-title":"Inflammation Bowel Dis"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines3010148","article-title":"Choice and design of adjuvants for parenteral and mucosal vaccines","volume":"3","author":"Savelkoul","year":"2015","journal-title":"Vaccines (Basel)"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00718.x","article-title":"Inflammatory signals in dendritic cell activation and the induction of adaptive immunity","volume":"227","author":"Joffre","year":"2009","journal-title":"Immunol Rev"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/srep19570","article-title":"Different human vaccine adjuvants promote distinct antigen-independent immunological signatures tailored to different pathogens","volume":"6","author":"Knudsen","year":"2016","journal-title":"Sci Rep"},{"key":"B14","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.imlet.2009.10.005","article-title":"The ABC of clinical and experimental adjuvants--a brief overview","volume":"128","author":"Brunner","year":"2010","journal-title":"Immunol Lett"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.4.519","article-title":"Requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment, and host defense","volume":"194","author":"Ye","year":"2001","journal-title":"J Exp Med"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.11.7980","article-title":"TLR4 mediates vaccine-induced protective cellular immunity to Bordetella pertussis: role of IL-17-producing T cells","volume":"177","author":"Higgins","year":"2006","journal-title":"J Immunol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0901584","article-title":"IL-17\/Th17 promotes type 1 T cell immunity against pulmonary intracellular bacterial infection through modulating dendritic cell function","volume":"183","author":"Bai","year":"2009","journal-title":"J Immunol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.07.035","article-title":"The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells","volume":"126","author":"Ivanov","year":"2006","journal-title":"Cell"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa4282","article-title":"Impairment of immunity to Candida and Mycobacterium in humans with bi-allelic RORC mutations","volume":"349","author":"Okada","year":"2015","journal-title":"Science"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201141569","article-title":"IL-23-dependent IL-17 drives Th1-cell responses following Mycobacterium bovis BCG vaccination","volume":"42","author":"Gopal","year":"2012","journal-title":"Eur J Immunol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/ni1449","article-title":"IL-23 and IL-17 in the establishment of protective pulmonary CD4+ T cell responses after vaccination and during Mycobacterium tuberculosis challenge","volume":"8","author":"Khader","year":"2007","journal-title":"Nat Immunol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-021-00163-y","article-title":"Emerging concepts in the science of vaccine adjuvants","volume":"20","author":"Pulendran","year":"2021","journal-title":"Nat Rev Drug Discov"},{"key":"B23","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.bbamem.2005.10.011","article-title":"Characterization of cationic liposomes based on dimethyldioctadecylammonium and synthetic cord factor from M. tuberculosis (trehalose 6,6\u2019-dibehenate)-a novel adjuvant inducing both strong CMI and antibody responses","volume":"1718","author":"Davidsen","year":"2005","journal-title":"Biochim Biophys Acta"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20091750","article-title":"Direct recognition of the mycobacterial glycolipid, trehalose dimycolate, by C-type lectin Mincle","volume":"206","author":"Ishikawa","year":"2009","journal-title":"J Exp Med"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0904013","article-title":"Cutting edge: Mincle is essential for recognition and adjuvanticity of the mycobacterial cord factor and its synthetic analog trehalose-dibehenate","volume":"184","author":"Schoenen","year":"2010","journal-title":"J Immunol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1084\/jem.20081445","article-title":"Adjuvanticity of a synthetic cord factor analogue for subunit Mycobacterium tuberculosis vaccination requires FcRgamma-Syk-Card9-dependent innate immune activation","volume":"206","author":"Werninghaus","year":"2009","journal-title":"J Exp Med"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1203343","article-title":"Cord factor and peptidoglycan recapitulate the Th17-promoting adjuvant activity of mycobacteria through mincle\/CARD9 signaling and the inflammasome","volume":"190","author":"Shenderov","year":"2013","journal-title":"J Immunol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxy028","article-title":"Mincle: 20 years of a versatile sensor of insults","volume":"30","author":"Lu","year":"2018","journal-title":"Int Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2012.04.004","article-title":"Mincle and human B cell function","volume":"39","author":"Kawata","year":"2012","journal-title":"J Autoimmun"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.17033","article-title":"Macrophage-inducible C-type lectin activates B cells to promote T cell reconstitution in heart allograft recipients","volume":"22","author":"Hasgur","year":"2022","journal-title":"Am J Transplant"},{"key":"B31","doi-asserted-by":"publisher","first-page":"2406","DOI":"10.1038\/s41467-022-30174-1","article-title":"TH17 cells promote CNS inflammation by sensing danger signals via Mincle","volume":"13","author":"Zhang","year":"2022","journal-title":"Nat Commun"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.163.9.5039","article-title":"A novel LPS-inducible C-type lectin is a transcriptional target of NF-IL6 in macrophages","volume":"163","author":"Matsumoto","year":"1999","journal-title":"J Immunol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1301593","article-title":"Differential control of Mincle-dependent cord factor recognition and macrophage responses by the transcription factors C\/EBP\u03b2 and HIF1\u03b1","volume":"193","author":"Schoenen","year":"2014","journal-title":"J Immunol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2000420","article-title":"Cutting edge: TNF is essential for mycobacteria-induced MINCLE expression, macrophage activation, and th17 adjuvanticity","volume":"205","author":"Schick","year":"2020","journal-title":"J Immunol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1093\/jleuko\/qiad029","article-title":"TNF promotes DECTIN2 family C-type lectin receptor expression in human macrophages","volume":"113","author":"Haberkamp","year":"2023","journal-title":"J Leukoc Biol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/nature04753","article-title":"Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells","volume":"441","author":"Bettelli","year":"2006","journal-title":"Nature"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2006.01.001","article-title":"TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells","volume":"24","author":"Veldhoen","year":"2006","journal-title":"Immunity"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/nature04754","article-title":"Transforming growth factor-beta induces development of the T(H)17 lineage","volume":"441","author":"Mangan","year":"2006","journal-title":"Nature"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.02.007","article-title":"Critical regulation of early Th17 cell differentiation by interleukin-1 signaling","volume":"30","author":"Chung","year":"2009","journal-title":"Immunity"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/ni1539","article-title":"TGF-beta and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain T(H)-17 cell-mediated pathology","volume":"8","author":"McGeachy","year":"2007","journal-title":"Nat Immunol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1172\/JCI65624","article-title":"Safe TNF-based antitumor therapy following p55TNFR reduction in intestinal epithelium","volume":"123","author":"van Hauwermeiren","year":"2013","journal-title":"J Clin Invest"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/srep22454","article-title":"Innate myeloid cell TNFR1 mediates first line defence against primary Mycobacterium tuberculosis infection","volume":"6","author":"Segueni","year":"2016","journal-title":"Sci Rep"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.5.2773-2778.2001","article-title":"Protection of mice with a tuberculosis subunit vaccine based on a fusion protein of antigen 85b and esat-6","volume":"69","author":"Weinrich Olsen","year":"2001","journal-title":"Infect Immun"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1023\/a:1008942828960","article-title":"Conditional gene targeting in macrophages and granulocytes using LysMcre mice","volume":"8","author":"Clausen","year":"1999","journal-title":"Transgenic Res"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.07.014","article-title":"Genetic tracing via DNGR-1 expression history defines dendritic cells as a hematopoietic lineage","volume":"154","author":"Schraml","year":"2013","journal-title":"Cell"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20062648","article-title":"Notch-RBP-J signaling controls the homeostasis of CD8- dendritic cells in the spleen","volume":"204","author":"Caton","year":"2007","journal-title":"J Exp Med"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-4141(199807)28:07<2159:AID-IMMU2159>3.0.CO;2-B","article-title":"Functional competence of T cells in the absence of glycosylphosphatidylinositol-anchored proteins caused by T cell-specific disruption of thePig-agene","volume":"28","author":"Takahama","year":"1998","journal-title":"Eur J Immunol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1402429","article-title":"C-type lectin receptor MCL facilitates mincle expression and signaling through complex formation","volume":"194","author":"Miyake","year":"2015","journal-title":"J Immunol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.11.7404","article-title":"The macrophage-inducible C-type lectin, mincle, is an essential component of the innate immune response to Candida albicans","volume":"180","author":"Wells","year":"2008","journal-title":"J Immunol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830271020","article-title":"Distinct roles for lymphotoxin-alpha and tumor necrosis factor in organogenesis and spatial organization of lymphoid tissue","volume":"27","author":"K\u00f6rner","year":"1997","journal-title":"Eur J Immunol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1038\/nature14452","article-title":"Th17 cells transdifferentiate into regulatory T cells during resolution of inflammation","volume":"523","author":"Gagliani","year":"2015","journal-title":"Nature"},{"key":"B52","doi-asserted-by":"publisher","first-page":"e3116","DOI":"10.1371\/journal.pone.0003116","article-title":"Cationic liposomes formulated with synthetic mycobacterial cordfactor (CAF01): a versatile adjuvant for vaccines with different immunological requirements","volume":"3","author":"Agger","year":"2008","journal-title":"PloS One"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.9.e45","article-title":"A new mathematical model for relative quantification in real-time RT-PCR","volume":"29","author":"Pfaffl","year":"2001","journal-title":"Nucleic Acids Res"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2024.103174","article-title":"Repeated immunization with ATRA-containing liposomal adjuvant transdifferentiates Th17 cells to a Tr1-like phenotype","volume":"144","author":"W\u00f8rzner","year":"2024","journal-title":"J Autoimmun"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.579761","article-title":"Vaccine adjuvants differentially affect kinetics of antibody and germinal center responses","volume":"11","author":"Pedersen","year":"2020","journal-title":"Front Immunol"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1021\/mp100208f","article-title":"Comparison of the depot effect and immunogenicity of liposomes based on dimethyldioctadecylammonium (DDA), 3\u03b2-N-(N\u2019,N\u2019-Dimethylaminoethane)carbomyl cholesterol (DC-Chol), and 1,2-Dioleoyl-3-trimethylammonium propane (DOTAP): prolonged liposome retention mediates stronger Th1 responses","volume":"8","author":"Henriksen-Lacey","year":"2011","journal-title":"Mol Pharm"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2012.03.016","article-title":"A cationic vaccine adjuvant based on a saturated quaternary ammonium lipid have different in vivo distribution kinetics and display a distinct CD4 T cell-inducing capacity compared to its unsaturated analog","volume":"160","author":"Christensen","year":"2012","journal-title":"J Control Release"},{"key":"B58","first-page":"76","article-title":"Tumor necrosis factor receptor-1 signaling is required for differentiation of follicular dendritic cells, germinal center formation, and full antibody responses","volume":"47","author":"Le Hir","year":"1995","journal-title":"J Inflammation"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.880474","article-title":"Monocytes elicit a neutrophil-independent th1\/th17 response upon immunization with a mincle-dependent glycolipid adjuvant","volume":"13","author":"Desel","year":"2022","journal-title":"Front Immunol"},{"key":"B60","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.coi.2020.09.001","article-title":"Cytokines and transcription factors in the differentiation of CD4+ T helper cell subsets and induction of tissue inflammation and autoimmunity","volume":"67","author":"Pawlak","year":"2020","journal-title":"Curr Opin Immunol"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1038\/ni1254","article-title":"Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages","volume":"6","author":"Harrington","year":"2005","journal-title":"Nat Immunol"},{"key":"B62","doi-asserted-by":"publisher","first-page":"e53531","DOI":"10.1371\/journal.pone.0053531","article-title":"The Mincle-activating adjuvant TDB induces MyD88-dependent Th1 and Th17 responses through IL-1R signaling","volume":"8","author":"Desel","year":"2013","journal-title":"PloS One"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.10.018","article-title":"Human inflammatory dendritic cells induce Th17 cell differentiation","volume":"38","author":"Segura","year":"2013","journal-title":"Immunity"},{"key":"B64","doi-asserted-by":"publisher","first-page":"1761","DOI":"10.1016\/j.immuni.2023.07.001","article-title":"Dendritic cell type 3 arises from Ly6C+ monocyte-dendritic cell progenitors","volume":"56","author":"Liu","year":"2023","journal-title":"Immunity"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2023.113600","article-title":"Variegate expression of Cre recombinase in hematopoietic cells in CD11c-cre transgenic mice","volume":"525","author":"Murat","year":"2024","journal-title":"J Immunol Methods"},{"key":"B66","doi-asserted-by":"publisher","first-page":"eadg5678","DOI":"10.1126\/scisignal.adg5678","article-title":"TNF-\u03b1 signals through ITK-Akt-mTOR to drive CD4+ T cell metabolic reprogramming, which is dysregulated in rheumatoid arthritis","volume":"17","author":"Bishop","year":"2024","journal-title":"Sci Signal"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1186\/ar3824","article-title":"Inhibition of Th17 differentiation by anti-TNF-alpha therapy in uveitis patients with Beh\u00e7et\u2019s disease","volume":"14","author":"Sugita","year":"2012","journal-title":"Arthritis Res Ther"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0303112","article-title":"Regulation of TCR-mediated T cell activation by TNF-RII","volume":"74","author":"Aspalter","year":"2003","journal-title":"J Leukoc Biol"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2109972118","article-title":"TNF plays a crucial role in inflammation by signaling via T cell TNFR2","volume":"118","author":"Alam","year":"2021","journal-title":"PNAS"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/385352","article-title":"TNF\u03b1 promotes Th17 cell differentiation through IL-6 and IL-1\u03b2 produced by monocytes in rheumatoid arthritis","volume":"2014","author":"Zheng","year":"2014","journal-title":"J Immunol Res"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.3.1449","article-title":"TNF-alpha drives human CD14+ monocytes to differentiate into CD70+ dendritic cells evoking Th1 and Th17 responses","volume":"179","author":"Iwamoto","year":"2007","journal-title":"J Immunol"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1002\/art.34565","article-title":"Th17 cells are restrained by Treg cells via the inhibition of interleukin-6 in patients with rheumatoid arthritis responding to anti-tumor necrosis factor antibody therapy","volume":"64","author":"McGovern","year":"2012","journal-title":"Arthritis Rheum"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1084\/jem.184.4.1397","article-title":"Immune and inflammatory responses in TNF alpha-deficient mice: a critical requirement for TNF alpha in the formation of primary B cell follicles, follicular dendritic cell networks and germinal centers, and in the maturation of the humoral immune response","volume":"184","author":"Pasparakis","year":"1996","journal-title":"J Exp Med"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-10-249177","article-title":"Cellular source and molecular form of TNF specify its distinct functions in organization of secondary lymphoid organs","volume":"116","author":"Tumanov","year":"2010","journal-title":"Blood"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1084\/jem.183.5.2367","article-title":"Differentiation of follicular dendritic cells and full antibody responses require tumor necrosis factor receptor-1 signaling","volume":"183","author":"Le Hir","year":"1996","journal-title":"J Exp Med"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1126\/science.271.5253.1289","article-title":"Role of lymphotoxin and the type I TNF receptor in the formation of germinal centers","volume":"271","author":"Matsumoto","year":"1996","journal-title":"Science"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065x.1997.tb00965.x","article-title":"Lymphotoxin-alpha-deficient and TNF receptor-I-deficient mice define developmental and functional characteristics of germinal centers","volume":"156","author":"Matsumoto","year":"1997","journal-title":"Immunol Rev"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1009234107","article-title":"Proinflammatory T helper type 17 cells are effective B-cell helpers","volume":"107","author":"Mitsdoerffer","year":"2010","journal-title":"PNAS"},{"key":"B79","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1038\/s41541-023-00781-0","article-title":"Co-adjuvanting DDA\/TDB liposomes with a TLR7 agonist allows for IgG2a\/c class-switching in the absence of Th1 cells","volume":"8","author":"Zimmermann","year":"2023","journal-title":"NPJ Vaccines"},{"key":"B80","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1093\/infdis\/jiad608","article-title":"Ectopic expression of C-type lectin mincle renders mice susceptible to staphylococcal pneumonia","volume":"230","author":"Hollwedel","year":"2024","journal-title":"J Infect Dis"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2000509","article-title":"Overexpression of macrophage-inducible C-type lectin mincle aggravates proinflammatory responses to streptococcus pneumoniae with fatal outcome in mice","volume":"205","author":"Hollwedel","year":"2020","journal-title":"J Immunol"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1651","article-title":"Mincle is an ITAM-coupled activating receptor that senses damaged cells","volume":"9","author":"Yamasaki","year":"2008","journal-title":"Nat Immunol"},{"key":"B83","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-024-52863-9","article-title":"MINCLE and TLR9 agonists synergize to induce Th1\/Th17 vaccine memory and mucosal recall in mice and non-human primates","volume":"15","author":"Woodworth","year":"2024","journal-title":"Nat Commun"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-023-00666-2","article-title":"A protective, single-visit TB vaccination regimen by co-administration of a subunit vaccine with BCG","volume":"8","author":"Dijkman","year":"2023","journal-title":"NPJ Vaccines"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20071087","article-title":"Alum adjuvant boosts adaptive immunity by inducing uric acid and activating inflammatory dendritic cells","volume":"205","author":"Kool","year":"2008","journal-title":"J Exp Med"},{"key":"B86","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1038\/nm.2403","article-title":"DNA released from dying host cells mediates aluminum adjuvant activity","volume":"17","author":"Marichal","year":"2011","journal-title":"Nat Med"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1618133114","article-title":"Intracellular metabolite \u03b2-glucosylceramide is an endogenous Mincle ligand possessing immunostimulatory activity","volume":"114","author":"Nagata","year":"2017","journal-title":"PNAS"},{"key":"B88","doi-asserted-by":"publisher","first-page":"e1006038","DOI":"10.1371\/journal.ppat.1006038","article-title":"C-type lectin mincle recognizes glucosyl-diacylglycerol of streptococcus pneumoniae and plays a protective role in pneumococcal pneumonia","volume":"12","author":"Behler-Janbeck","year":"2016","journal-title":"PloS Pathog"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.21203\/rs.3.rs-7495259\/v1","article-title":"TNF promotes Th17 vaccine responses by enabling myeloid cell pattern recognition via Mincle","author":"Blamberg","year":"2025","journal-title":"Res Square"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1746618\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T05:22:49Z","timestamp":1770614569000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1746618\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,9]]},"references-count":89,"alternative-id":["10.3389\/fimmu.2026.1746618"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1746618","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,9]]},"article-number":"1746618"}}