{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T15:46:44Z","timestamp":1791733604821,"version":"4.3.4"},"reference-count":41,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82473407"],"award-info":[{"award-number":["82473407"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82573619"],"award-info":[{"award-number":["82573619"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Anim Models and Exp Med"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Lymph node (LN) fibrosis occurs in a variety of pathological conditions, including HIV infection, obesity, cancer, and tissue injury. Fibroblastic reticular cells (FRCs) play a critical role in maintaining LN architecture and immune homeostasis, whereas their dysregulation promotes extracellular matrix (ECM) deposition and immune dysfunction. Transforming growth factor\u2010\u03b21 (TGF\u2010\u03b21) is a key profibrotic cytokine. However, reliable and convenient animal models for investigating LN fibrosis remain limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study comprehensively compared four induction methods: footpad injection of TGF\u2010\u03b21, lymphatic vessel ligation, inguinal subcutaneous injection of TGF\u2010\u03b21, and direct intra\u2010LN injection of TGF\u2010\u03b21. Histological analysis, transcriptomic profiling, flow cytometric analysis, and safety evaluation were performed to assess fibrosis and immune alterations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among the four approaches, inguinal subcutaneous and intra\u2010LN injection of TGF\u2010\u03b21 successfully induced LN fibrosis without causing significant injury to major organs. Notably, the intra\u2010LN injection model induced fibrosis in both cortical and medullary regions of LNs. Comparing the transcriptomic data of fibrotic and non\u2010fibrotic LNs demonstrated marked changes in fibrosis\u2010related genes, including pro\u2010fibrogenic mediators, collagens and basement membrane\u2010related genes, and TGF\u2010\u03b21\u2010associated signaling pathways. In two fibrotic models, we also noticed increased macrophage infiltration and a drop in CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells, suggesting an immune suppressive microenvironment. Furthermore, inhibition of collagen cross\u2010linking partially alleviated fibrotic remodeling in fibrotic LNs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We established and characterized two mouse models of LN fibrosis induced by TGF\u2010\u03b21 administration. These models provide valuable tools for investigating the mechanisms of LN fibrosis and its impact on local immune regulation, and may facilitate the development of therapeutic strategies targeting fibrotic LNs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ame2.70261","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T11:57:08Z","timestamp":1785758228000},"page":"1782-1794","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Establishment and characterization of mouse lymph node fibrosis models"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7880-4007","authenticated-orcid":false,"given":"Yaru","family":"Niu","sequence":"first","affiliation":[{"name":"Department of Colorectal Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical 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