{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:45:08Z","timestamp":1787021108895,"version":"build-2736575974"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T00:00:00Z","timestamp":1709510400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T00:00:00Z","timestamp":1709510400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Key Laboratory of Infection and Immunity of Anhui Higher Education Institutes","award":["AHIAI2022R04"],"award-info":[{"award-number":["AHIAI2022R04"]}]},{"DOI":"10.13039\/501100010814","name":"Department of Education Anhui Province","doi-asserted-by":"crossref","award":["2022AH051494"],"award-info":[{"award-number":["2022AH051494"]}],"id":[{"id":"10.13039\/501100010814","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Adv Rheumatol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The labial salivary glands (LSGs) are important for the diagnosis, evaluation of therapeutic efficacy, and genetic analyses of primary Sj\u00f6gren\u2019s syndrome (pSS). In autoimmune diseases, the recognition of self nucleic acids and viral RNA and DNA through endogenous Toll-like receptor(TLR) triggers the production of type I IFN and pro-inflammatory cytokines, leading to the occurrence and progression of the disease. Here, we detected the expression of TLR7 in LSGs and analyse its correlation with clinical features and serum cytokines in pSS patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>LSGs and serum samples were obtained from 56 pSS patients and 19 non-SS patients (non-pSS patients). The expression of TLR7 in the LSGs was evaluated with immunohistochemistry. The serum levels of interferon-\u03b1 (IFN-\u03b1) and interleukin-6 (IL-6) were quantified by ELISA. Laboratory parameters were measured by clinical standard laboratory techniques.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>TLR7-positive cells in pSS were localized in the ductal epithelial cells and lymphocytes of LSGs. The expression of TLR7 was upregulated in pSS patients compared with controls. Patients with anti-Ro52 antibody positivity showed higher TLR7 levels than those who were negative but not those with anti-Ro60 and anti-SSB. TLR7 levels were positively associated with the levels of IgG, IgA, ANA, IL-6, IFN-\u03b1 and serum globulin but were not associated with IgM, C3, C4, or rheumatoid factor (RF) in serum.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>TLR7 may be involved in the inflammatory response and the production of antibodies in pSS and plays an important role in local and systemic pSS manifestations. This research showed that TLR7 is involved in pSS pathogenesis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s42358-024-00360-4","type":"journal-article","created":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T06:01:51Z","timestamp":1709532111000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Elevated expression of Toll-like receptor 7 and its correlation with clinical features in patients with primary Sj\u00f6gren\u2019s syndrome"],"prefix":"10.1186","volume":"64","author":[{"given":"Huimin","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changhao","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5328-6370","authenticated-orcid":false,"given":"Zhijun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,4]]},"reference":[{"issue":"10","key":"360_CR1","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1056\/NEJMcp1702514","volume":"378","author":"X Mariette","year":"2018","unstructured":"Mariette X, Criswell LA. Primary Sj\u00f6gren\u2019s syndrome. N Engl J Med. 2018;378(10):931\u20139.","journal-title":"N Engl J Med"},{"key":"360_CR2","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.clim.2017.03.007","volume":"182","author":"AV Goules","year":"2017","unstructured":"Goules AV, Kapsogeorgou EK, Tzioufas AG. Insight into pathogenesis of Sj\u00f6gren\u2019s syndrome: dissection on autoimmune infiltrates and epithelial cells. Clin Immunol. 2017;182:30\u201340.","journal-title":"Clin Immunol"},{"issue":"5","key":"360_CR3","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1097\/BOR.0000000000000195","volume":"27","author":"A Ambrosi","year":"2015","unstructured":"Ambrosi A, Wahren-Herlenius M. Update on the immunobiology of Sj\u00f6gren\u2019s syndrome. Curr Opin Rheumatol. 2015;27(5):468\u201375.","journal-title":"Curr Opin Rheumatol"},{"issue":"6","key":"360_CR4","doi-asserted-by":"publisher","first-page":"2561","DOI":"10.1093\/rheumatology\/key360","volume":"60","author":"ILA Bodewes","year":"2021","unstructured":"Bodewes ILA, Bj\u00f6rk A, Versnel MA, Wahren-Herlenius M. Innate immunity and interferons in the pathogenesis of Sj\u00f6gren\u2019s syndrome. Rheumatology (Oxford). 2021;60(6):2561\u201373.","journal-title":"Rheumatology (Oxford)"},{"issue":"1","key":"360_CR5","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1111\/cei.13242","volume":"196","author":"T Shimizu","year":"2019","unstructured":"Shimizu T, Nakamura H, Takatani A, Umeda M, Horai Y, Kurushima S, Michitsuji T, Nakashima Y, Kawakami A. Activation of toll-like receptor 7 signaling in labial salivary glands of primary Sj\u00f6gren\u2019s syndrome patients. Clin Exp Immunol. 2019;196(1):39\u201351.","journal-title":"Clin Exp Immunol"},{"issue":"6","key":"360_CR6","doi-asserted-by":"publisher","first-page":"1044","DOI":"10.1016\/j.cell.2020.02.041","volume":"180","author":"KA Fitzgerald","year":"2020","unstructured":"Fitzgerald KA, Kagan JC. Toll-like receptors and the control of immunity. Cell. 2020;180(6):1044\u201366.","journal-title":"Cell"},{"key":"360_CR7","doi-asserted-by":"publisher","first-page":"676010","DOI":"10.3389\/fimmu.2021.676010","volume":"12","author":"Y Wang","year":"2021","unstructured":"Wang Y, Roussel-Queval A, Chasson L, Hanna Kazazian N, Marcadet L, Nezos A, Sieweke MH, Mavragani C, Alexopoulou L. TLR7 Signaling drives the development of Sj\u00f6gren\u2019s syndrome. Front Immunol. 2021;12:676010.","journal-title":"Front Immunol"},{"issue":"7909","key":"360_CR8","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1038\/s41586-022-04642-z","volume":"605","author":"GJ Brown","year":"2022","unstructured":"Brown GJ, Ca\u00f1ete PF, Wang H, Medhavy A, Bones J, Roco JA, He Y, Qin Y, Cappello J, Ellyard JI, et al. TLR7 gain-of-function genetic variation causes human lupus. Nature. 2022;605(7909):349\u201356.","journal-title":"Nature"},{"issue":"2","key":"360_CR9","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1038\/s41584-020-00544-4","volume":"17","author":"S Fillatreau","year":"2021","unstructured":"Fillatreau S, Manfroi B, D\u00f6rner T. Toll-like receptor signalling in B cells during systemic lupus erythematosus. Nat Rev Rheumatol. 2021;17(2):98\u2013108.","journal-title":"Nat Rev Rheumatol"},{"issue":"5","key":"360_CR10","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1097\/BOR.0000000000000310","volume":"28","author":"M Teruel","year":"2016","unstructured":"Teruel M, Alarc\u00f3n-Riquelme ME. Genetics of systemic lupus erythematosus and Sj\u00f6gren\u2019s syndrome: an update. Curr Opin Rheumatol. 2016;28(5):506\u201314.","journal-title":"Curr Opin Rheumatol"},{"issue":"1","key":"360_CR11","doi-asserted-by":"publisher","first-page":"3523","DOI":"10.1038\/s41467-021-23472-7","volume":"12","author":"P Soret","year":"2021","unstructured":"Soret P, Le Dantec C, Desvaux E, Foulquier N, Chassagnol B, Hubert S, Jamin C, Barturen G, Desachy G, Devauchelle-Pensec V, et al. A new molecular classification to drive precision treatment strategies in primary Sj\u00f6gren\u2019s syndrome. Nat Commun. 2021;12(1):3523.","journal-title":"Nat Commun"},{"issue":"12","key":"360_CR12","doi-asserted-by":"publisher","first-page":"1991","DOI":"10.1002\/art.42265","volume":"74","author":"D Trutschel","year":"2022","unstructured":"Trutschel D, Bost P, Mariette X, Bondet V, Llibre A, Posseme C, Charbit B, Thorball CW, Jonsson R, Lessard CJ, et al. Variability of primary Sj\u00f6gren\u2019s syndrome is driven by Interferon-\u03b1 and Interferon-\u03b1 blood levels are Associated with the class II HLA-DQ locus. Arthritis Rheumatol. 2022;74(12):1991\u20132002.","journal-title":"Arthritis Rheumatol"},{"issue":"1","key":"360_CR13","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1002\/art.39859","volume":"69","author":"CH Shiboski","year":"2017","unstructured":"Shiboski CH, Shiboski SC, Seror R, Criswell LA, Labetoulle M, Lietman TM, Rasmussen A, Scofield H, Vitali C, Bowman SJ, et al. 2016 American College of Rheumatology\/European League against Rheumatism Classification Criteria for Primary Sj\u00f6gren\u2019s syndrome: a Consensus and Data-Driven Methodology Involving Three International Patient cohorts. Arthritis Rheumatol. 2017;69(1):35\u201345.","journal-title":"Arthritis Rheumatol"},{"issue":"7","key":"360_CR14","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.1136\/annrheumdis-2016-210448","volume":"76","author":"BA Fisher","year":"2017","unstructured":"Fisher BA, Jonsson R, Daniels T, Bombardieri M, Brown RM, Morgan P, Bombardieri S, Ng WF, Tzioufas AG, Vitali C, et al. Standardisation of labial salivary gland histopathology in clinical trials in primary Sj\u00f6gren\u2019s syndrome. Ann Rheum Dis. 2017;76(7):1161\u20138.","journal-title":"Ann Rheum Dis"},{"issue":"4","key":"360_CR15","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1007\/s10238-020-00637-0","volume":"20","author":"FJ Carrillo-Ballesteros","year":"2020","unstructured":"Carrillo-Ballesteros FJ, Palafox-S\u00e1nchez CA, Franco-Topete RA, Mu\u00f1oz-Valle JF, Orozco-Barocio G, Mart\u00ednez-Bonilla GE, G\u00f3mez-L\u00f3pez CE, Mar\u00edn-Rosales M, L\u00f3pez-Villalobos EF, Luquin S, et al. Expression of BAFF and BAFF receptors in primary Sj\u00f6gren\u2019s syndrome patients with ectopic germinal center-like structures. Clin Exp Med. 2020;20(4):615\u201326.","journal-title":"Clin Exp Med"},{"issue":"7","key":"360_CR16","doi-asserted-by":"publisher","first-page":"2021","DOI":"10.1002\/art.30381","volume":"63","author":"TE Daniels","year":"2011","unstructured":"Daniels TE, Cox D, Shiboski CH, Schi\u00f8dt M, Wu A, Lanfranchi H, Umehara H, Zhao Y, Challacombe S, Lam MY, et al. Associations between salivary gland histopathologic diagnoses and phenotypic features of Sj\u00f6gren\u2019s syndrome among 1,726 registry participants. Arthritis Rheum. 2011;63(7):2021\u201330.","journal-title":"Arthritis Rheum"},{"issue":"5","key":"360_CR17","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1016\/j.autrev.2012.10.006","volume":"12","author":"Y Yao","year":"2013","unstructured":"Yao Y, Liu Z, Jallal B, Shen N, R\u00f6nnblom L. Type I interferons in Sj\u00f6gren\u2019s syndrome. Autoimmun Rev. 2013;12(5):558\u201366.","journal-title":"Autoimmun Rev"},{"issue":"5","key":"360_CR18","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1097\/BOR.0000000000000524","volume":"30","author":"GE Thorlacius","year":"2018","unstructured":"Thorlacius GE, Wahren-Herlenius M, R\u00f6nnblom L. An update on the role of type I interferons in systemic lupus erythematosus and Sj\u00f6gren\u2019s syndrome. Curr Opin Rheumatol. 2018;30(5):471\u201381.","journal-title":"Curr Opin Rheumatol"},{"key":"360_CR19","doi-asserted-by":"publisher","first-page":"980400","DOI":"10.3389\/fimmu.2022.980400","volume":"13","author":"L Alexopoulou","year":"2022","unstructured":"Alexopoulou L. Nucleic acid-sensing toll-like receptors: important players in Sj\u00f6gren\u2019s syndrome. Front Immunol. 2022;13:980400.","journal-title":"Front Immunol"},{"key":"360_CR20","doi-asserted-by":"publisher","first-page":"985729","DOI":"10.3389\/fimmu.2022.985729","volume":"13","author":"M Xiang","year":"2022","unstructured":"Xiang M, Wang Y, Gao Z, Wang J, Chen Q, Sun Z, Liang J, Xu J. Exploring causal correlations between inflammatory cytokines and systemic lupus erythematosus: a mendelian randomization. Front Immunol. 2022;13:985729.","journal-title":"Front Immunol"},{"issue":"11","key":"360_CR21","doi-asserted-by":"publisher","first-page":"e1008142","DOI":"10.1371\/journal.ppat.1008142","volume":"15","author":"Z Luo","year":"2019","unstructured":"Luo Z, Su R, Wang W, Liang Y, Zeng X, Shereen MA, Bashir N, Zhang Q, Zhao L, Wu K, et al. EV71 infection induces neurodegeneration via activating TLR7 signaling and IL-6 production. PLoS Pathog. 2019;15(11):e1008142.","journal-title":"PLoS Pathog"},{"issue":"3","key":"360_CR22","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1136\/annrheumdis-2020-218467","volume":"80","author":"R Felten","year":"2021","unstructured":"Felten R, Devauchelle-Pensec V, Seror R, Duffau P, Saadoun D, Hachulla E, Pierre Yves H, Salliot C, Perdriger A, Morel J, et al. Interleukin 6 receptor inhibition in primary Sj\u00f6gren syndrome: a multicentre double-blind randomised placebo-controlled trial. Ann Rheum Dis. 2021;80(3):329\u201338.","journal-title":"Ann Rheum Dis"},{"key":"360_CR23","doi-asserted-by":"publisher","first-page":"281","DOI":"10.3389\/fimmu.2019.00281","volume":"10","author":"R Davies","year":"2019","unstructured":"Davies R, Sarkar I, Hammenfors D, Bergum B, Vogelsang P, Solberg SM, Gavasso S, Brun JG, Jonsson R, Appel S. Single cell based phosphorylation profiling identifies alterations in toll-like receptor 7 and 9 signaling in patients with primary Sj\u00f6gren\u2019s syndrome. Front Immunol. 2019;10:281.","journal-title":"Front Immunol"},{"key":"360_CR24","doi-asserted-by":"publisher","first-page":"1034336","DOI":"10.3389\/fimmu.2022.1034336","volume":"13","author":"A Punnanitinont","year":"2022","unstructured":"Punnanitinont A, Kasperek EM, Kiripolsky J, Zhu C, Miecznikowski JC, Kramer JM. TLR7 agonism accelerates disease in a mouse model of primary Sj\u00f6gren\u2019s syndrome and drives expansion of T-bet(+) B cells. Front Immunol. 2022;13:1034336.","journal-title":"Front Immunol"},{"issue":"1","key":"360_CR25","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1002\/jcp.30923","volume":"238","author":"ZH Wang","year":"2023","unstructured":"Wang ZH, Feng Y, Hu Q, Wang XL, Zhang L, Liu TT, Zhang JT, Yang X, Fu QY, Fu DN, et al. Keratinocyte TLR2 and TLR7 contribute to chronic itch through pruritic cytokines and chemokines in mice. J Cell Physiol. 2023;238(1):257\u201373.","journal-title":"J Cell Physiol"},{"issue":"9","key":"360_CR26","doi-asserted-by":"publisher","first-page":"2427","DOI":"10.1002\/art.39214","volume":"67","author":"E Theander","year":"2015","unstructured":"Theander E, Jonsson R, Sj\u00f6str\u00f6m B, Brokstad K, Olsson P, Henriksson G. Prediction of Sj\u00f6gren\u2019s Syndrome years before diagnosis and identification of patients with early onset and severe Disease Course by Autoantibody Profiling. Arthritis Rheumatol. 2015;67(9):2427\u201336.","journal-title":"Arthritis Rheumatol"},{"issue":"17","key":"360_CR27","doi-asserted-by":"publisher","first-page":"1854","DOI":"10.1001\/jama.2013.278448","volume":"310","author":"R Jonsson","year":"2013","unstructured":"Jonsson R, Theander E, Sj\u00f6str\u00f6m B, Brokstad K, Henriksson G. Autoantibodies present before symptom onset in primary Sj\u00f6gren syndrome. JAMA. 2013;310(17):1854\u20135.","journal-title":"JAMA"},{"issue":"3","key":"360_CR28","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1136\/ard-2022-222728","volume":"82","author":"AP Lopes","year":"2023","unstructured":"Lopes AP, Hillen MR, Hinrichs AC, Blokland SL, Bekker CP, Pandit A, Kruize AA, Radstake TR, van Roon JA. Deciphering the role of cDC2s in Sj\u00f6gren\u2019s syndrome: transcriptomic profile links altered antigen processes with IFN signature and autoimmunity. Ann Rheum Dis. 2023;82(3):374\u201383.","journal-title":"Ann Rheum Dis"}],"container-title":["Advances in Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s42358-024-00360-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s42358-024-00360-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s42358-024-00360-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T06:02:25Z","timestamp":1709532145000},"score":1,"resource":{"primary":{"URL":"https:\/\/advancesinrheumatology.biomedcentral.com\/articles\/10.1186\/s42358-024-00360-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,4]]},"references-count":28,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["360"],"URL":"https:\/\/doi.org\/10.1186\/s42358-024-00360-4","relation":{},"ISSN":["2523-3106"],"issn-type":[{"value":"2523-3106","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,4]]},"assertion":[{"value":"14 August 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 February 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 March 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was approved by the Research Ethics Committee of the Second Affiliated Hospital of Bengbu Medical College (2023BYEFY-5\u00a0A).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"17"}}