{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T11:50:42Z","timestamp":1785757842399,"version":"3.56.0"},"reference-count":65,"publisher":"Wiley","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":["82130032"],"award-info":[{"award-number":["82130032"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Chronic pain is sustained by complex neuroimmune interplay within the spinal cord, yet how astrocytes constrain immune amplification remains poorly understood. Here we identified Src\u2010homology 2 domain\u2010containing protein tyrosine phosphatase\u20101 (SHP1; encoded by\n                    <jats:italic>Ptpn6<\/jats:italic>\n                    ) as a key suppressor of spinal neuroinflammation and nociceptive hypersensitivity. Astrocyte\u2010specific SHP1 deletion in the spinal dorsal horn induced profound astrocytic morphological changes, increased C\u2010X\u2010C motif chemokine ligand 10 (CXCL10) expression, disrupted blood\u2010brain barrier (BBB) integrity, and facilitated the infiltration of activated T lymphocytes into the spinal parenchyma. These infiltrating T cells promoted microglial activation, enhanced excitatory synaptic transmission, increased the excitability of somatostatin (SOM)\u2010positive neurons, and ultimately triggered nociceptive hypersensitivity. Mechanistically, T cell recruitment was governed by an SHP1\u2010dependent regulatory circuit, in which SHP1\u2010mediated Signal transducer and activator of transcription 1 (STAT1) dephosphorylation restrained\n                    <jats:italic>Cxcl10<\/jats:italic>\n                    transcription. Blocking the STAT1\u2013CXCL10\u2013CXCR3 signaling axis alleviated T cell infiltration and nociceptive hypersensitivity. Notably, we found that during the development of neuropathic pain, spinal SHP1 expression was significantly downregulated, accompanied by upregulation of CXCL10. Overexpression of SHP1 in astrocytes markedly attenuated astrocyte activation and alleviated mechanical allodynia induced by spared nerve injury (SNI). Collectively, our findings revealed an astrocyte\u2010defined immune checkpoint that restrains neuroinflammatory escalation and pain persistence, emphasizing SHP1 as a promising therapeutic target for chronic pain.\n                  <\/jats:p>","DOI":"10.1002\/advs.76932","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T11:41:49Z","timestamp":1785757309000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Loss of SHP1 in Spinal Astrocytes Triggers T\u2010Lymphocyte Infiltration and Nociceptive Hypersensitivity"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-3150-1292","authenticated-orcid":false,"given":"Lan\u2010Xing","family":"Yi","sequence":"first","affiliation":[{"name":"Department of Translational Neuroscience Jing'an District Centre Hospital of Shanghai State Key Laboratory of Brain Function and Disorders and MOE Frontiers Center For Brain Science Institutes of Brain Science Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Translational Neuroscience Jing'an District Centre Hospital of Shanghai State Key Laboratory of Brain Function and Disorders and MOE Frontiers Center For Brain Science Institutes of Brain Science Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4125-1718","authenticated-orcid":false,"given":"Kang\u2010Li","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Translational Neuroscience Jing'an District Centre Hospital of Shanghai State Key Laboratory of Brain Function and Disorders and MOE Frontiers Center For Brain Science Institutes of Brain Science Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5909-692X","authenticated-orcid":false,"given":"Hui\u2010Zhu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Translational Neuroscience Jing'an District Centre Hospital of Shanghai State Key Laboratory of Brain Function and Disorders and MOE Frontiers Center For Brain Science Institutes of Brain Science Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui\u2010Ying","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Huadong Hospital; Key Laboratory of Computational Neuroscience and Brain\u2010Inspired Intelligence Ministry of Education; Behavioral and Cognitive Neuroscience Center Institute of Science and Technology for Brain\u2010Inspired Intelligence MOE Frontiers Center for Brain Science Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3589-9573","authenticated-orcid":false,"given":"Min","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Pathology and Pathophysiology Shantou University Medical College  Shantou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4328-0634","authenticated-orcid":false,"given":"Xiao","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Huadong Hospital; Key Laboratory of Computational Neuroscience and Brain\u2010Inspired Intelligence Ministry of Education; Behavioral and Cognitive Neuroscience Center Institute of Science and Technology for Brain\u2010Inspired Intelligence MOE Frontiers Center for Brain Science Fudan University  Shanghai 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