{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T05:07:21Z","timestamp":1779944841356,"version":"3.53.1"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>This study investigates the pathogenic contributions of aquaporin-4 (AQP4)-specific follicular helper T (Tfh) and T helper 17 (Th17) cells in neuromyelitis optica spectrum disorder (NMOSD), utilizing newly established murine models based on adoptive transfer of antigen-specific T-cell populations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>AQP4-knockout mice were immunized with the AQP4-derived peptide to generate AQP4-reactive Tfh and Th17 cells. These cells were subsequently isolated and adoptively transferred into wild-type recipient mice. At disease peak\u2014defined by consistent neurological deficits\u2014spinal cord and brain tissues were harvested for histopathological analysis, as well as immunohistochemistry. Central nervous system immune cell infiltration was quantified via flow cytometry. Total RNA was extracted from spinal cord tissue for bulk RNA sequencing; differentially expressed genes were validated using quantitative real-time PCR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Recipient mice that received AQP4-reactive Tfh or Th17 cells developed progressive hind-limb weakness, with Th17-transferred mice exhibiting significantly more severe clinical scores. Histopathological analyses revealed robust perivascular inflammation, parenchymal immune infiltration, and focal demyelination. Immunohistochemical quantification demonstrated significantly increased the optical density of CD3, B220, GFAP, IBA1, and CXCL9, alongside markedly decreased MBP expression. Flow cytometric profiling confirmed substantial infiltration of leukocytes and activated microglia\/macrophages into the central nervous system (CNS). Transcriptomic analysis identified CXCL9 as one of the most upregulated chemokines in the spinal cord; its astrocytic origin was further corroborated by confocal immunofluorescence co-localization with GFAP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our findings establish that AQP4-specific Tfh and Th17 cells are sufficient to drive key neuropathological features of NMOSD\u2014including microglial reactivity, leukocyte recruitment, neuroinflammation, and demyelination\u2014\n                      <jats:italic>in vivo<\/jats:italic>\n                      . The pronounced upregulation and astrocyte-derived expression of CXCL9 suggest its involvement in orchestrating CNS inflammation and position it as a potential contributor for NMOSD.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1704040","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T04:57:04Z","timestamp":1779944224000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["CXCL9 associates with experimental neuromyelitis optica spectrum disorder following adoptive transfer of Tfh and Th17 cells"],"prefix":"10.3389","volume":"17","author":[{"given":"Liang","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neurology and Rare Disease Center, Huashan Hospital, Shanghai Medical College, Fudan University","place":["Shanghai, China"]},{"name":"National Center for Neurological Disorders","place":["Shanghai, 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