{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:45:37Z","timestamp":1790739937122,"version":"4.1.0"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005230","name":"Natural Science Foundation of Chongqing Municipality","doi-asserted-by":"publisher","award":["CSTB2025NSCQ-GPX0455"],"award-info":[{"award-number":["CSTB2025NSCQ-GPX0455"]}],"id":[{"id":"10.13039\/501100005230","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017501","name":"Science-Health Joint Medical Scientific Research Project of Chongqing","doi-asserted-by":"publisher","award":["2026MSXM099"],"award-info":[{"award-number":["2026MSXM099"]}],"id":[{"id":"10.13039\/100017501","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Impaired microglial clearance of amyloid-\u03b2 (A\u03b2) is a central driver of Alzheimer's disease (AD), yet the mechanisms governing intracellular A\u03b2 degradation remain poorly defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We investigated the role of CD22 in microglial A\u03b2 processing using primary microglia, transcriptomic profiling, and hippocampal samples from AD patients and transgenic mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified CD22 as an A\u03b2-inducible signaling regulator that restrains microglial A\u03b2 processing. CD22 expression was elevated in the hippocampus of AD patients and transgenic mice and was rapidly induced by A\u03b2 in microglia. Functionally,\n                      <jats:italic>CD22<\/jats:italic>\n                      knockdown enhanced intracellular A\u03b2 degradation without affecting initial uptake. Transcriptomic profiling identified the AD risk gene INPP5D as a key downstream effector of CD22. Loss of\n                      <jats:italic>CD22<\/jats:italic>\n                      suppressed INPP5D expression and promoted AKT activation, while INPP5D overexpression partially rescued the enhanced A\u03b2 clearance phenotype. These findings define a CD22-INPP5D signaling axis that acts as a molecular brake on microglial A\u03b2 processing. A\u03b2 itself induces CD22 expression, revealing a feed-forward inhibitory loop in which amyloid accumulation limits its own clearance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Collectively, these findings identify a regulatory mechanism controlling intracellular A\u03b2 degradation and suggest the CD22-INPP5D axis as a potential therapeutic target for AD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fncel.2026.1886995","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T04:26:19Z","timestamp":1785212779000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["CD22 regulates A\u03b2 clearance in microglia through INPP5D signaling"],"prefix":"10.3389","volume":"20","author":[{"given":"De-Zhi","family":"Zou","sequence":"first","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[{"name":"Brain Research Center and State Key Laboratory of Trauma, Burns, and Combined Injury, The Army Medical University (Third Military Medical University)","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiu-Shuang","family":"Long","sequence":"additional","affiliation":[{"name":"Institute of Advanced Pathology Research","place":["Jinfeng Laboratory, Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruo-Qi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Advanced Pathology Research","place":["Jinfeng Laboratory, Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing-Lin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Institute of Advanced Pathology Research","place":["Jinfeng Laboratory, Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Ze","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"684430","DOI":"10.3389\/fimmu.2021.684430","article-title":"CD22 blockage restores age-related impairments of microglia surveillance capacity","volume":"12","author":"Aires","year":"2021","journal-title":"Front. 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