{
  "abstract": "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‐homology 2 domain‐containing protein tyrosine phosphatase‐1 (SHP1; encoded by Ptpn6) as a key suppressor of spinal neuroinflammation and nociceptive hypersensitivity. Astrocyte‐specific SHP1 deletion in the spinal dorsal horn induced profound astrocytic morphological changes, increased C‐X‐C motif chemokine ligand 10 (CXCL10) expression, disrupted blood‐brain 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)‐positive neurons, and ultimately triggered nociceptive hypersensitivity. Mechanistically, T cell recruitment was governed by an SHP1‐dependent regulatory circuit, in which SHP1‐mediated Signal transducer and activator of transcription 1 (STAT1) dephosphorylation restrained Cxcl10 transcription. Blocking the STAT1–CXCL10–CXCR3 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‐defined immune checkpoint that restrains neuroinflammatory escalation and pain persistence, emphasizing SHP1 as a promising therapeutic target for chronic pain.",
  "abstract_shown": true,
  "affiliations": [
    "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",
    "Department of Endocrinology Huadong Hospital; Key Laboratory of Computational Neuroscience and Brain‐Inspired Intelligence Ministry of Education; Behavioral and Cognitive Neuroscience Center Institute of Science and Technology for Brain‐Inspired Intelligence MOE Frontiers Center for Brain Science Fudan University Shanghai China",
    "Department of Pathology and Pathophysiology Shantou University Medical College Shantou China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Lan‐Xing Yi",
      "orcid": "0009-0001-3150-1292"
    },
    {
      "affs": [
        0
      ],
      "name": "Lin Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "Kang‐Li Wang",
      "orcid": "0009-0008-4125-1718"
    },
    {
      "affs": [
        0
      ],
      "name": "Hui‐Zhu Liu",
      "orcid": "0009-0001-5909-692X"
    },
    {
      "affs": [
        1
      ],
      "name": "Rui‐Ying Chen"
    },
    {
      "affs": [
        2
      ],
      "name": "Min Su",
      "orcid": "0000-0003-3589-9573"
    },
    {
      "affs": [
        1
      ],
      "name": "Xiao Xiao",
      "orcid": "0000-0002-4328-0634"
    },
    {
      "affs": [
        0
      ],
      "name": "Yu‐Qiu Zhang",
      "orcid": "0000-0001-6623-9629"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/306m20p4ktdxx.bib",
  "cited_by": 0,
  "doi": "10.1002/advs.76932",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13430923/",
  "id": "306m20p4ktdxx",
  "issns": [
    "2198-3844"
  ],
  "landing_url": "https://doi.org/10.1002/advs.76932",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "2737|Pain Mechanisms and Treatments"
    ]
  ],
  "openalex": "W7172291791",
  "pdf_url": null,
  "pmcid": "PMC13430923",
  "pmid": "42545195",
  "published": "2026-08-03",
  "publisher": "Wiley",
  "ris": "https://research.draconitic.com/paper/306m20p4ktdxx.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:23:40Z",
      "native_id": "PMC13430923",
      "source": "pmc",
      "url": "https://doi.org/10.1002/advs.76932"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2737|Pain Mechanisms and Treatments",
      "subfield": "physiology"
    }
  ],
  "title": "Loss of SHP1 in Spinal Astrocytes Triggers T‐Lymphocyte Infiltration and Nociceptive Hypersensitivity",
  "title_text": "Loss of SHP1 in Spinal Astrocytes Triggers T‐Lymphocyte Infiltration and Nociceptive Hypersensitivity",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:20:48Z",
  "url": "https://research.draconitic.com/paper/306m20p4ktdxx",
  "venue": "Advanced Science",
  "versions": []
}