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Astrocytes are among the primary cell types rapidly activated to produce various chemokines immediately after SCI. However, the molecular mechanisms regulating the expression of astrocytic chemokines, particularly the inflammation\u2010related chemokine C\u2010C motif ligand 7 (CCL7), remain elusive. D\u2010dopachrome tautomerase (D\u2010DT, also known as MIF\u20102), a member of the macrophage migration inhibitory factor (MIF) family, has been shown to deteriorate the inflammatory milieu and worsen neurological outcomes following SCI. In this study, CCL7 was dramatically induced in astrocytes following SCI and contributed to the accumulation of microglia\/macrophages at lesion sites. In\u00a0vitro experiments demonstrated that astrocyte\u2010derived CCL7 significantly promoted microglia\/macrophages migration through coupling with chemokine C\u2010C motif receptor 2 (CCR2). Blocking of CCL7 with a neutralizing antibody or administering a CCR2 inhibitor substantially ameliorated tissue damage and promoted locomotor recovery. Further mechanistic investigation revealed that the D\u2010DT\/CD74 axis enhanced astrocytic CCL7 production by activating the MAPKs\/NF\u2010\u03baB and IL\u20106\/STAT3 signaling pathways. Treatment with the D\u2010DT pharmacological inhibitor 4\u2010CPPC reduced astrocytic CCL7 production and consequently limited microglia\/macrophages accumulation at lesion sites after SCI. These findings uncover a novel regulatory pathway for astrocyte\u2010derived CCL7 production and highlight its detrimental role in neurological recovery, which might provide new clues for clinical treatment of neuroinflammation after SCI.<\/jats:p>","DOI":"10.1096\/fj.202500902r","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T14:26:05Z","timestamp":1763389565000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["D\u2010Dopachrome Tautomerase\u2010Driven Astrocytic\n                    <scp>CCL7<\/scp>\n                    Aggravates Neuropathology by Recruitment of Microglia Following Spinal Cord Injury"],"prefix":"10.1096","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0489-2814","authenticated-orcid":false,"given":"Honghua","family":"Song","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory of Tissue Engineering and Neuroregeneration, Key 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