{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T13:36:56Z","timestamp":1788356216140,"version":"build-2803163510"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"vor","delay-in-days":14,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81301973"],"award-info":[{"award-number":["81301973"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Science and Technology Commission Foundation of Shanghai","award":["14JC1492500"],"award-info":[{"award-number":["14JC1492500"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Blood Res."],"published-print":{"date-parts":[[2026,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>An immune-mediated pathogenesis has been postulated for aplastic anemia (AA), and impaired Tregs and other immune abnormalities have been identified in patients with AA. However, the process by which abnormal immunity specifically damages hematopoietic stem cells (HSCs) remains unclear. We conducted primary clinical studies to investigate whether the depletion of HSCs in AA could be attributed to the collapse of immune privilege (IP) afforded by regulatory T cells (Tregs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The distribution of Tregs in the bone marrow of children with AA, myelodysplastic syndrome (MDS), and control participants was separately detected by immunohistochemistry. T-helper 1 (Th1), T-helper 2 (Th2), and T-helper 17 (Th17) cells, cytokines, and HSCs in the bone marrow of the AA and control groups were examined using flow cytometry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Patients with AA showed significantly lower FoxP3\u2009+\u2009\/CD4\u2009+\u2009ratios (AA\n                      <jats:italic>vs<\/jats:italic>\n                      . normal: 18.09%\u2009\u00b1\u20095.38%\n                      <jats:italic>vs<\/jats:italic>\n                      . 21.72%\u2009\u00b1\u20094.21%,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.014; AA\n                      <jats:italic>vs.<\/jats:italic>\n                      MDS: 18.09%\u2009\u00b1\u20095.38%\n                      <jats:italic>vs<\/jats:italic>\n                      . 22.63%\u2009\u00b1\u20095.98%,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.030) and reduced Treg counts (AA\n                      <jats:italic>vs<\/jats:italic>\n                      . normal: 4.07\u2009\u00b1\u20091.41\n                      <jats:italic>vs<\/jats:italic>\n                      . 5.25\u2009\u00b1\u20091.86 cells\/HP,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.014; AA\n                      <jats:italic>vs.<\/jats:italic>\n                      MDS: 4.07\u2009\u00b1\u20091.41\n                      <jats:italic>vs<\/jats:italic>\n                      . 5.30\u2009\u00b1\u20091.49 cells\/HP,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.024) near the endosteum. The bone marrow in patients with AA exhibited Th1 dominance (AA\n                      <jats:italic>vs<\/jats:italic>\n                      . normal: 39.80%\u2009\u00b1\u20095.20%\n                      <jats:italic>vs<\/jats:italic>\n                      . 22.1%\u2009\u00b1\u20092.9% in controls,\u00a0\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001) and Th2 reduction (AA\n                      <jats:italic>vs<\/jats:italic>\n                      . normal: 59.20%\u2009\u00b1\u20095.30%\n                      <jats:italic>vs<\/jats:italic>\n                      . 77.20%\u2009\u00b1\u20092.60%,\u00a0\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001), indicating IP dysfunction. Significant elevation of tumor necrosis factor (TNF)-\u03b1, interferon (IFN)-\u03b3, and interleukin (IL)-17 levels was observed in the bone marrow of patients with AA. Long-term (LT)-HSCs were severely depleted in patients with AA (AA\n                      <jats:italic>vs<\/jats:italic>\n                      . normal: 0.13%\n                      <jats:italic>vs<\/jats:italic>\n                      . 1.22%,\u00a0\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.035), with moderate reduction in short-term (ST)-HSCs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Patients with AA showed endosteal Treg reduction, Th1 dominance, elevated proinflammatory cytokine levels, and severe LT-HSC depletion, linking bone marrow IP dysfunction to HSC damage. These findings provide a mechanistic explanation for the specific loss of HSCs in AA and highlight the IP niche as a therapeutic target.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s44313-026-00141-6","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T01:13:08Z","timestamp":1779757988000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The role of impaired bone marrow Tregs in hematopoietic stem cell depletion for pediatric aplastic anemia probably involves immune privilege"],"prefix":"10.1007","volume":"61","author":[{"given":"Can","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwei","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangyang","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanyi","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shayi","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"141_CR1","doi-asserted-by":"publisher","first-page":"186","DOI":"10.3389\/fimmu.2017.00186","volume":"8","author":"JL Espinoza","year":"2017","unstructured":"Espinoza JL, Kotecha R, Nakao S. 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