{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T22:59:59Z","timestamp":1779317999295,"version":"3.51.4"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["RO1 CA194042"],"award-info":[{"award-number":["RO1 CA194042"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Autoimmune hypophysitis is classified as primary if its origin is idiopathic and secondary if it develops as a consequence of treatment with immune checkpoint inhibitors. Expanding use of immunotherapy has been paralleled by the increasing hypophysitis prevalence. However, understanding of the immune responses driving the disease remains limited. Using a mouse model of primary hypophysitis, we have identified CD4+ T lymphocytes to be the main pituitary-infiltrating immune cell population. Functional analysis showed that they display a Th17 and Th1\/Th17 phenotype. To examine involvement of proinflammatory Th1, Th17, and Th1\/17 subsets in hypophysitis, we have isolated RNA from the formalin-fixed paraffin-embedded pituitary specimens from 16 hypophysitis patients (three of whom had hypophysitis secondary to immune checkpoint inhibitors), 10 patients with adenoma, and 23 normal pituitaries obtained at autopsy. Transcript levels of IFN-\u03b3, IL-17A, IL-4, IL-10, TGF-\u03b2, CD4, CD8\u03b1, and class II MHC transactivator were analyzed by the reverse transcription\u2013quantitative PCR (RT-qPCR). Pituitary glands of patients with hypophysitis showed significantly higher IL-17A, CD4, and class II MHC transactivator mRNA levels compared with adenoma and normal pituitaries. All three secondary hypophysitis patients showed detectable IL-17A levels, but other cytokines were not detected in their pituitaries. Levels of IFN-\u03b3, IL-4, IL-10, and TGF-\u03b2 did not differ between the groups. TGF-\u03b2 transcript was found in significantly fewer hypophysitis pituitaries (2 out of 16) compared with adenoma (7 out of 10) and normal pituitaries (11 out of 23). Presence of TGF-\u03b2 in two hypophysitis patients was associated with significantly lower IL-17A mRNA levels compared with hypophysitis patients with no detectable TGF-\u03b2 (p = 0.03).<\/jats:p>","DOI":"10.4049\/jimmunol.2001073","type":"journal-article","created":{"date-parts":[[2021,5,19]],"date-time":"2021-05-19T19:05:29Z","timestamp":1621451129000},"page":"2536-2543","source":"Crossref","is-referenced-by-count":21,"title":["Th17 Cells Contribute to the Pathology of Autoimmune Hypophysitis"],"prefix":"10.1093","volume":"206","author":[{"given":"Paulina","family":"Chalan","sequence":"first","affiliation":[{"name":"Division of Immunology, Department of Pathology, The Johns Hopkins School of Medicine , Baltimore, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nithya","family":"Thomas","sequence":"additional","affiliation":[{"name":"Division of Immunology, Department of Pathology, The Johns Hopkins School of Medicine , Baltimore, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6768-6308","authenticated-orcid":false,"given":"Patrizio","family":"Caturegli","sequence":"additional","affiliation":[{"name":"Division of Immunology, Department of Pathology, The Johns Hopkins School of Medicine , Baltimore, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,6,1]]},"reference":[{"key":"2025030417503655300_r1","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/nrendo.2013.212","article-title":"Endocrine autoimmune diseases and female infertility","volume":"10","author":"Sen","year":"2014","journal-title":"Nat. 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Metab."},{"key":"2025030417503655300_r6","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/nrendo.2016.205","article-title":"Cancer immunotherapy - immune checkpoint blockade and associated endocrinopathies","volume":"13","author":"Byun","year":"2017","journal-title":"Nat. Rev. Endocrinol."},{"key":"2025030417503655300_r7","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1210\/jc.2007-0808","article-title":"Autoimmune hypophysitis: an underestimated disease in search of its autoantigen(s)","volume":"92","author":"Caturegli","year":"2007","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"2025030417503655300_r8","doi-asserted-by":"crossref","first-page":"22246","DOI":"10.1073\/pnas.1908079116","article-title":"Autoimmune antibodies correlate with immune checkpoint therapy-induced toxicities","volume":"116","author":"Tahir","year":"2019","journal-title":"Proc. Natl. Acad. Sci. 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Endocrinol."},{"key":"2025030417503655300_r11","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1530\/EJE-11-1015","article-title":"Identification of TPIT and other novel autoantigens in lymphocytic hypophysitis: immunoscreening of a pituitary cDNA library and development of immunoprecipitation assays","volume":"166","author":"Smith","year":"2012","journal-title":"Eur. J. Endocrinol."},{"key":"2025030417503655300_r12","first-page":"609","article-title":"Cytosolic autoantigens in lymphocytic hypophysitis","volume":"83","author":"Crock","year":"1998","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"2025030417503655300_r13","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1210\/jcem.87.2.8205","article-title":"Identification of the 49-kDa autoantigen associated with lymphocytic hypophysitis as alpha-enolase","volume":"87","author":"O\u2019Dwyer","year":"2002","journal-title":"J. Clin. Endocrinol. 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