{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:53:24Z","timestamp":1792799604419,"version":"4.5.0"},"reference-count":69,"publisher":"American Society for Clinical Investigation","issue":"4","license":[{"start":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T00:00:00Z","timestamp":1677024000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Seed Fund for Basic Research, University Research Committee, The University of Hong Kong","award":["157344,"],"award-info":[{"award-number":["157344,"]}],"id":[{"id":"https:\/\/ror.org\/02zhqgq86","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Health & Medical Research Fund, Food and Health Bureau, Hong Kong","award":["09201006"],"award-info":[{"award-number":["09201006"]}],"id":[{"id":"https:\/\/ror.org\/03qh32912","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,2,22]]},"abstract":"<jats:p>\n                    Neuromyelitis optica spectrum disorders (NMOSD) are inflammatory autoimmune disorders of the CNS. IgG autoantibodies targeting the aquaporin-4 water channel (AQP4-IgGs) are the pathogenic effector of NMOSD. Dysregulated T follicular helper (Tfh) cells have been implicated in loss of B cell tolerance in autoimmune diseases. The contribution of Tfh cells to disease activity and therapeutic potential of targeting these cells in NMOSD remain unclear. Here, we established an autoimmune model of NMOSD by immunizing mice against AQP4 via in vivo electroporation. After AQP4 immunization, mice displayed AQP4 autoantibodies in blood circulation, blood-brain barrier disruption, and IgG infiltration in spinal cord parenchyma. Moreover, AQP4 immunization induced motor impairments and NMOSD-like pathologies, including astrocytopathy, demyelination, axonal loss, and microglia activation. These were associated with increased splenic Tfh, Th1, and Th17 cells; memory B cells; and plasma cells.\n                    <jats:italic>Aqp4<\/jats:italic>\n                    -deficient mice did not display motor impairments and NMOSD-like pathologies after AQP4 immunization. Importantly, abrogating ICOS\/ICOS-L signaling using anti\u2013ICOS-L antibody depleted Tfh cells and suppressed the response of Th1 and Th17 cells, memory B cells, and plasma cells in AQP4-immunized mice. These findings were associated with ameliorated motor impairments and spinal cord pathologies. This study suggests a role of Tfh cells in the pathophysiology of NMOSD in a mouse model with AQP4 autoimmunity and provides an animal model for investigating the immunological mechanisms underlying AQP4 autoimmunity and developing therapeutic interventions targeting autoimmune reactions in NMOSD.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.161003","type":"journal-article","created":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T12:00:27Z","timestamp":1673956827000},"source":"Crossref","is-referenced-by-count":23,"title":["T follicular helper cells contribute to pathophysiology in a model of neuromyelitis optica spectrum disorders"],"prefix":"10.1172","volume":"8","author":[{"given":"Leung-Wah","family":"Yick","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4415-3936","authenticated-orcid":true,"given":"Oscar 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