{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T16:01:15Z","timestamp":1789488075185,"version":"build-2803163510"},"reference-count":72,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30CA023168"],"award-info":[{"award-number":["P30CA023168"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["P20DK140417"],"award-info":[{"award-number":["P20DK140417"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01\u2010DK126478"],"award-info":[{"award-number":["R01\u2010DK126478"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Benign prostatic hyperplasia (BPH) is the most common urologic disease in aging men, resulting in significant morbidity. The etiologies of BPH are unknown, though chronic prostatic inflammation is known to promote hyperplasia, fibrotic remodeling, and therapeutic resistance in BPH. BPH is highly complex and heterogeneous, presenting with varying degrees of stromal and epithelial proliferation, fibrosis, inflammation, and associated lower urinary tract symptoms. This complexity poses challenges in developing models. Here, we characterize an\n                    <jats:italic>Aire<\/jats:italic>\n                    transcription factor\u2010deficient nonresolving (chronic) inflammation model in a C57BL\/6J background for the study of the prostatic inflammation present in BPH. This chronic inflammatory model exhibits a lack of central tolerance but retains an otherwise intact and functional immune system. C57BL\/6\n                    <jats:sup>\n                      <jats:italic>Aire<\/jats:italic>\n                      \u2212\/\u2212\n                    <\/jats:sup>\n                    mice were subcutaneously injected with prostate homogenate protein and Freund's Complete Adjuvant and boosted after 10\u2009days. After 21 and 35\u2009days, whole prostates were collected for histology, flow cytometry, and single\u2010cell RNA sequencing (scRNA\u2010seq), which were then compared to human BPH data. Inflammation was confined to the prostate in C57BL\/6\n                    <jats:sup>\n                      <jats:italic>Aire<\/jats:italic>\n                      \u2212\/\u2212\n                    <\/jats:sup>\n                    mice. Histological and scRNA\u2010seq data show that the dominant leukocyte phenotypes in the prostates of C57BL\/6\n                    <jats:sup>\n                      <jats:italic>Aire<\/jats:italic>\n                      \u2212\/\u2212\n                    <\/jats:sup>\n                    mice are B and T lymphocytes. Macrophages in C57BL\/6\n                    <jats:sup>\n                      <jats:italic>Aire<\/jats:italic>\n                      \u2212\/\u2212\n                    <\/jats:sup>\n                    mouse prostates express signatures associated with an array of phenotypes, as also seen in BPH. We identify a\n                    <jats:italic>Trem2<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    population of macrophages and aging\u2010associated Cd8\n                    <jats:sup>+<\/jats:sup>\n                    <jats:italic>GZMK<\/jats:italic>\n                    hi\n                    <jats:italic>GZMB<\/jats:italic>\n                    low T cells in C57BL\/6\n                    <jats:sup>\n                      <jats:italic>Aire<\/jats:italic>\n                      \u2212\/\u2212\n                    <\/jats:sup>\n                    prostates similar to those seen in human BPH. Further, fibroblast clusters in C57BL\/6\n                    <jats:sup>\n                      <jats:italic>Aire<\/jats:italic>\n                      \u2212\/\u2212\n                    <\/jats:sup>\n                    are similar to fibroblasts identified from the prostates of patients diagnosed with BPH, and these clusters also express markers associated with aging. Overall, the inflammation and predicted leukocyte\u2010\u2010stromal interactions observed in the prostates of C57BL\/6\n                    <jats:sup>\n                      <jats:italic>Aire<\/jats:italic>\n                      \u2212\/\u2212\n                    <\/jats:sup>\n                    mice resemble human BPH, likely at the early stages of the disease, making this model useful for studying the impact of inflammation\u2010driven prostatic hyperplasia. \u00a9 2026 The Author(s).\n                    <jats:italic>The Journal of Pathology<\/jats:italic>\n                    published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.70093","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T03:28:22Z","timestamp":1783567702000},"page":"211-225","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immune dysregulation in the prostates of\n                    <scp>C57BL<\/scp>\n                    \/\n                    <scp>6<\/scp>\n                    <sup>\n                      <i>Aire<\/i>\n                      \u2212\/\u2212\n                    <\/sup>\n                    mice mirrors that seen in human benign prostatic hyperplasia"],"prefix":"10.1002","volume":"270","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1819-7070","authenticated-orcid":false,"given":"Nadia A","family":"Lanman","sequence":"first","affiliation":[{"name":"Department of Comparative Pathobiology Purdue University  West Lafayette IN USA"},{"name":"Purdue University Institute for Cancer Research Purdue University  West Lafayette IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meaghan M","family":"Broman","sequence":"additional","affiliation":[{"name":"Department of Comparative Pathobiology Purdue University  West Lafayette IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0759-4601","authenticated-orcid":false,"given":"Harish","family":"Kothandaraman","sequence":"additional","affiliation":[{"name":"Purdue University Institute for Cancer Research Purdue University  West Lafayette IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory M","family":"Cresswell","sequence":"additional","affiliation":[{"name":"Department of Comparative Pathobiology Purdue University  West Lafayette IN USA"},{"name":"Purdue University Institute for Cancer Research Purdue University  West Lafayette IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gada D","family":"Awdalkreem","sequence":"additional","affiliation":[{"name":"Department of Comparative Pathobiology Purdue University  West Lafayette IN USA"},{"name":"Purdue University Institute for Cancer Research Purdue University  West Lafayette IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilinaer","family":"Wusiman","sequence":"additional","affiliation":[{"name":"Department of Comparative Pathobiology Purdue University  West Lafayette IN USA"},{"name":"Purdue University Institute for Cancer Research Purdue University  West Lafayette IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andree K","family":"Kolliegbo","sequence":"additional","affiliation":[{"name":"Purdue University Institute for Cancer Research Purdue University  West Lafayette IN USA"},{"name":"Department of Computer Science Purdue University  West Lafayette IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander P","family":"Glaser","sequence":"additional","affiliation":[{"name":"Division of Urology, Department of Surgery Endeavor Health Research Institute  Evanston IL USA"},{"name":"University of Chicago Pritzker School of Medicine  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian T","family":"Helfand","sequence":"additional","affiliation":[{"name":"Division of Urology, Department of Surgery Endeavor Health Research Institute  Evanston IL USA"},{"name":"University of Chicago Pritzker School of Medicine  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5614-9221","authenticated-orcid":false,"given":"Renee E","family":"Vickman","sequence":"additional","affiliation":[{"name":"University of Chicago Pritzker School of Medicine  Chicago IL USA"},{"name":"Department of Cancer Biology Endeavor Health Research Institute  Evanston IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Comparative Pathobiology Purdue University  West Lafayette IN USA"},{"name":"Purdue University Institute for Cancer Research Purdue University  West Lafayette IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon W","family":"Hayward","sequence":"additional","affiliation":[{"name":"University of Chicago Pritzker School of Medicine  Chicago IL USA"},{"name":"Department of Cancer Biology Endeavor Health Research Institute  Evanston IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy L","family":"Ratliff","sequence":"additional","affiliation":[{"name":"Department of Comparative Pathobiology Purdue University  West Lafayette IN USA"},{"name":"Purdue University Institute for Cancer Research Purdue University  West Lafayette IN 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