{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T13:40:55Z","timestamp":1792676455906,"version":"4.5.0"},"reference-count":166,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunol Cell Biol"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Aquaporin\u20104 (AQP4) antibody\u2010positive neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody\u2010associated disease (MOGAD) are distinct autoimmune inflammatory conditions of the central nervous system. Defined autoantigens characterize NMOSD and MOGAD; however, the mechanisms driving immune activation, tissue injury, and breakdown of immune tolerance differ substantially between these conditions. Both conditions reflect a breakdown of immune tolerance mechanisms, permitting the persistence and activation of autoreactive T and B cells. However, NMOSD is characterized by a more clearly defined antibody and complement\u2010mediated astrocytopathy, whereas MOGAD appears to require synergy with T\u2010cell\u2010driven inflammation, with a more variable contribution from complement\u2010mediated and innate effector pathways. This review summarizes the current understanding of innate and adaptive immune activation and mechanisms of immune tolerance failure in NMOSD and MOGAD and highlights how these features may inform emerging therapeutic strategies.<\/jats:p>","DOI":"10.1111\/imcb.70171","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T13:01:58Z","timestamp":1792674118000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Balance Between Immune Activation and Tolerance in\n                    <scp>AQP4<\/scp>\n                    Antibody\u2010Positive Neuromyelitis Optica Spectrum Disorders and\n                    <scp>MOG<\/scp>\n                    Antibody\u2010Associated Disease"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-7588-1658","authenticated-orcid":false,"given":"Morya","family":"Wadodkar","sequence":"first","affiliation":[{"name":"University of Bristol  Bristol UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0980-3750","authenticated-orcid":false,"given":"Saif","family":"Huda","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics University of Liverpool  Liverpool UK"},{"name":"Department of Neurology The Walton Centre NHS Foundation Trust  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1215-9583","authenticated-orcid":false,"given":"Chiara","family":"Rocchi","sequence":"additional","affiliation":[{"name":"Department of Neurology The Walton Centre NHS Foundation Trust  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,22]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","DOI":"10.3390\/ijms26125503","article-title":"Understanding the Immune System's Intricate Balance: Activation, Tolerance, and Self\u2010Protection","volume":"26","author":"Chen J.\u2010Y.","year":"2025","journal-title":"International Journal of Molecular Sciences"},{"key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/s00401-016-1606-5","article-title":"Vascular, Glial, and Lymphatic Immune Gateways of the Central Nervous System","volume":"132","author":"Engelhardt B.","year":"2016","journal-title":"Acta Neuropathologica"},{"key":"e_1_2_10_4_1","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1111\/bpa.12099","article-title":"The Pathology of an Autoimmune Astrocytopathy: Lessons Learned From Neuromyelitis Optica","volume":"24","author":"Lucchinetti C. 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