{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T12:41:27Z","timestamp":1777812087476,"version":"3.51.4"},"reference-count":27,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2015,3,17]],"date-time":"2015-03-17T00:00:00Z","timestamp":1426550400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Dent Res"],"published-print":{"date-parts":[[2015,5]]},"abstract":"<jats:p>\n                    The presence of functional autoantibodies against the muscarinic type 3 receptor (M3R) has been reported in primary Sj\u00f6gren\u2019s syndrome (pSS). However, the pathogenic role of these autoantibodies in pSS development remains to be elucidated. In this experiment, we investigated a pathologic role of pSS autoantibodies (pSS IgG) associated with downregulation of the major histocompatibility complex I (MHC I) molecule with M3R through internalization. Anti-M3R autoantibodies in purified control and pSS IgG were detected using 4 synthesized cyclic M3R peptides by enzyme-linked immunosorbent assay. The binding reactivity of pSS IgG to M3R in situ was analyzed by a dual immunostaining method. Surface expression, interaction, and internalization of M3R with MHC I were analyzed by immunofluorescence confocal microscopy and biochemical assays. Synthetic cyclic peptides M3RP\n                    <jats:sup>205-221<\/jats:sup>\n                    and M3RP\n                    <jats:sup>520-527<\/jats:sup>\n                    showed significantly high reactivity with pSS IgG compared to the control IgG or the other 3 peptides ( P &lt; 0.05). Significantly high reactivity of pSS IgG to M3R in situ was observed. PSS IgG increased the interaction of membrane M3R with MHC I and induced their internalization in primary human submandibular gland cells. The pSS IgG-induced internalization of M3R with MHC I was significantly inhibited by the cholesterol-sequestering drug filipin. Our novel finding\u2014namely, strong downregulation of the membrane MHC I with M3R through internalization of the cholesterol-rich microdomain associating with anti-M3R autoantibodies\u2014could be an important mechanism contributing to the impaired salivation seen in pSS and linking secretory hypofunction to autoimmune pathogenesis.\n                  <\/jats:p>","DOI":"10.1177\/0022034515577813","type":"journal-article","created":{"date-parts":[[2015,3,17]],"date-time":"2015-03-17T22:54:37Z","timestamp":1426632877000},"page":"722-728","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":16,"title":["Effect of Antimuscarinic Autoantibodies in Primary Sj\u00f6gren\u2019s Syndrome"],"prefix":"10.1177","volume":"94","author":[{"given":"N.","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Physiology, School of Dentistry, Seoul National University and Dental Research Institute, Seoul, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y.","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Dentistry, Seoul National University and Dental Research Institute, Seoul, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Dentistry, Seoul National University and Dental Research Institute, Seoul, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Namkoong","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Dentistry, Seoul National University and Dental Research Institute, Seoul, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Dentistry, Seoul National University and Dental Research Institute, Seoul, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Lee","sequence":"additional","affiliation":[{"name":"Oral and Maxillofacial Surgery, School of Dentistry, Seoul National University and Dental Research Institute, Seoul, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y.","family":"Song","sequence":"additional","affiliation":[{"name":"Internal Medicine, College of Medicine, Seoul National University, Seoul, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Dentistry, Seoul National University and Dental Research Institute, Seoul, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2015,3,17]]},"reference":[{"key":"bibr1-0022034515577813","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032712-095910"},{"key":"bibr2-0022034515577813","doi-asserted-by":"crossref","unstructured":"Caulfield MP. 1993. Muscarinic receptors: characterization, coupling and function. Pharmacol Ther. 58(3):319\u2013379.","DOI":"10.1016\/0163-7258(93)90027-B"},{"key":"bibr3-0022034515577813","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003226"},{"key":"bibr4-0022034515577813","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0033335"},{"key":"bibr5-0022034515577813","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keq420"},{"key":"bibr6-0022034515577813","doi-asserted-by":"publisher","DOI":"10.1016\/j.coms.2013.09.008"},{"key":"bibr7-0022034515577813","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2011.11.012"},{"key":"bibr8-0022034515577813","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-0825.2011.01853.x"},{"key":"bibr9-0022034515577813","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.039727"},{"key":"bibr10-0022034515577813","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ken064"},{"key":"bibr11-0022034515577813","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70324-2"},{"key":"bibr12-0022034515577813","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.23.021704.115526"},{"key":"bibr13-0022034515577813","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1101776"},{"key":"bibr14-0022034515577813","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0b013e32832eba21"},{"key":"bibr15-0022034515577813","doi-asserted-by":"publisher","DOI":"10.1002\/art.30282"},{"key":"bibr16-0022034515577813","doi-asserted-by":"crossref","unstructured":"Roberts JM. 2000. Angiotensin-1 receptor autoantibodies: a role in the pathogenesis of preeclampsia? Circulation. 101(20):2335\u20132337.","DOI":"10.1161\/01.CIR.101.20.2335"},{"key":"bibr17-0022034515577813","doi-asserted-by":"crossref","unstructured":"Routsias JG, Tzioufas AG. 2007. Sj\u00f6gren\u2019s syndrome: study of autoantigens and autoantibodies. 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