{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:43:10Z","timestamp":1791506590165,"version":"4.3.4"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,3,9]],"date-time":"2018-03-09T00:00:00Z","timestamp":1520553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Autoimmune hypophysitis (AH) is thought to be an autoimmune disease characterized by lymphocytic infiltration of the pituitary gland. Among AH pathologies, lymphocytic infundibulo\u2010neurohypophysitis (LINH) involves infiltration of the neurohypophysis and\/or the hypothalamic infundibulum, causing central diabetes insipidus resulting from insufficiency of arginine vasopressin secretion. The pathophysiological and pathogenetic mechanisms underlying LINH are largely unknown. Clinically, differentiating LINH from other pituitary diseases accompanied by mass lesions, including tumours, has often been difficult, because of similar clinical manifestations. We recently reported that rabphilin\u20103A is an autoantigen and that anti\u2010rabphilin\u20103A antibodies constitute a possible diagnostic marker for LINH. However, the involvement of rabphilin\u20103A in the pathogenesis of LINH remains to be elucidated. This study was undertaken to explore the role of rabphilin\u20103A in lymphocytic neurohypophysitis and to investigate the mechanism. We found that immunization of mice with rabphilin\u20103A led to neurohypophysitis. Lymphocytic infiltration was observed in the neurohypophysis and supraoptic nucleus 1 month after the first immunization. Mice immunized with rabphilin\u20103A showed an increase in the volume of urine that was hypotonic as compared with control mice. Administration of a cocktail of monoclonal anti\u2010rabphilin\u20103A antibodies did not induce neurohypophysitis. However, abatacept, which is a chimeric protein that suppresses T\u2010cell activation, decreased the number of T cells specific for rabphilin\u20103A in peripheral blood mononuclear cells (PBMCs). It ameliorated lymphocytic infiltration of CD3<jats:sup>+<\/jats:sup> T cells in the neurohypophysis of mice that had been immunized with rabphilin\u20103A. Additionally, there was a linear association between the number of T cells specific for rabphilin\u20103A in PBMCs and the number of CD3<jats:sup>+<\/jats:sup> T cells infiltrating the neurohypophysis. In conclusion, we suggest that rabphilin\u20103A is a pathogenic antigen, and that T cells specific for rabphilin\u20103A are involved in the pathogenesis of neurohypophysitis in mice. Copyright \u00a9 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.5046","type":"journal-article","created":{"date-parts":[[2018,1,29]],"date-time":"2018-01-29T16:56:04Z","timestamp":1517244964000},"page":"469-478","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Critical role of rabphilin\u20103A in the pathophysiology of experimental lymphocytic neurohypophysitis"],"prefix":"10.1002","volume":"244","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0098-9931","authenticated-orcid":false,"given":"Yoshinori","family":"Yasuda","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Diabetes Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shintaro","family":"Iwama","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes Nagoya University Graduate School of Medicine  Nagoya 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