{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T17:15:19Z","timestamp":1788455719669,"version":"build-2803163510"},"reference-count":39,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23KJ0671"],"award-info":[{"award-number":["23KJ0671"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Vet Pathol"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:p>\n                    Canine intestinal T-cell lymphoma (ITCL) may arise from intraepithelial lymphocyte (IEL) subsets expanded in chronic enteropathy (CE). To investigate this potential cell of origin, we performed flow cytometry, immunohistochemistry, and RNA\n                    <jats:italic toggle=\"yes\">in situ<\/jats:italic>\n                    hybridization on IELs using biopsy samples from 62 dogs, including 6 large-cell lymphomas (LCLs), 9 small-cell lymphomas (SCLs), 31 CEs with increased IELs (IEL\n                    <jats:sup>+<\/jats:sup>\n                    CE), and 16 CEs without increased IELs (IEL\n                    <jats:sup>\u2013<\/jats:sup>\n                    CE). IELs in ITCLs were predominantly CD4\n                    <jats:sup>\u2212<\/jats:sup>\n                    CD8\u03b1\n                    <jats:sup>\u2212<\/jats:sup>\n                    (LCL, 5\/6; SCL, 4\/9), and 4\/31 IEL\n                    <jats:sup>+<\/jats:sup>\n                    CEs had a higher proportion of CD4\n                    <jats:sup>\u2212<\/jats:sup>\n                    CD8\u03b1\n                    <jats:sup>\u2212<\/jats:sup>\n                    IELs than the other CE cases. Forward scatter values of CD4\n                    <jats:sup>\u2212<\/jats:sup>\n                    CD8\u03b1\n                    <jats:sup>\u2212<\/jats:sup>\n                    IELs were higher in IEL\n                    <jats:sup>+<\/jats:sup>\n                    CEs compared with IEL\n                    <jats:sup>\u2013<\/jats:sup>\n                    CEs, correlating positively with the Ki-67 index, indicating proliferation of this population. An increase in IELs lacking T-cell receptor expression was observed in 1\/4 LCL, 2\/5 SCL, and 1\/13 IEL\n                    <jats:sup>+<\/jats:sup>\n                    CE cases. Lack of surface CD3 was observed in 2\/9 SCL cases. One of 5 LCL cases partially expressed NKp46, whereas the proportion of NKp46\n                    <jats:sup>+<\/jats:sup>\n                    IELs was low (&lt; 4%) in 32\/33 CE cases examined. In addition, 3\/6 LCL cases expressed\n                    <jats:italic toggle=\"yes\">NKp46<\/jats:italic>\n                    mRNA without detectable protein expression. Clonality analysis of isolated IELs yielded at least 1 clonal peak in 1\/2 LCLs, 4\/7 SCLs, 12\/23 IEL\n                    <jats:sup>+<\/jats:sup>\n                    CEs, and 4\/13 IEL\n                    <jats:sup>\u2013<\/jats:sup>\n                    CEs, underscoring the limited diagnostic utility on distinguishing ITCL, particularly SCL, from IEL\n                    <jats:sup>+<\/jats:sup>\n                    CE. These findings suggest that most canine ITCLs have a CD4\n                    <jats:sup>\u2212<\/jats:sup>\n                    CD8\u03b1\n                    <jats:sup>\u2212<\/jats:sup>\n                    immunophenotype and that unconventional IELs in IEL\n                    <jats:sup>+<\/jats:sup>\n                    CE may be the cells of origin. Moreover, the distinction between ITCL and CE remains challenging, emphasizing the importance of integrated diagnostic approaches.\n                  <\/jats:p>","DOI":"10.1177\/03009858261428495","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T06:32:48Z","timestamp":1774938768000},"page":"853-864","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Comprehensive phenotypic and clonality analysis of intraepithelial lymphocytes of intestinal T-cell lymphoma and chronic enteropathy in dogs"],"prefix":"10.1177","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-0254-4979","authenticated-orcid":false,"given":"Kazuhiro","family":"Kojima","sequence":"first","affiliation":[{"name":"The University of Tokyo, Bunkyo-ku, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5273-7221","authenticated-orcid":false,"given":"James K.","family":"Chambers","sequence":"additional","affiliation":[{"name":"The University of Tokyo, Bunkyo-ku, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ko","family":"Nakashima","sequence":"additional","affiliation":[{"name":"Japan Small Animal Medical Center, Tokorozawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5228-7125","authenticated-orcid":false,"given":"Yuko","family":"Goto-Koshino","sequence":"additional","affiliation":[{"name":"The University of Tokyo, Bunkyo-ku, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuyuki","family":"Uchida","sequence":"additional","affiliation":[{"name":"The University of Tokyo, Bunkyo-ku, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,3,30]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12191"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetimm.2021.110305"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/jvim.17036"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2006.114512"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V94.1.260.413k40_260_264"},{"key":"e_1_3_3_7_2","unstructured":"Bhagat G Naresh KN Dave SS et al. Enteropathy-associated T-cell lymphoma. In: WHO Classification of Tumours Editorial Board ed. Haematolymphoid Tumours [Internet]. Lyon: International Agency for Research on Cancer; 2024. 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Tumors of the hemolymphatic system. In: Meuten DJ, ed. Tumors in Domestic Animals. 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