{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T09:05:13Z","timestamp":1780909513908,"version":"3.54.1"},"reference-count":51,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"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":["Brain and Behavior"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Neuromyelitis optica spectrum disorders (NMOSD) are an immune\u2010mediated inflammatory disease of the central nervous system (CNS) primarily characterized by anti\u2010aquaporin\u20104 immunoglobulin G (AQP4\u2010IgG)\u2010mediated astrocyte injury, neuroinflammation, and demyelination. However, the relationship between the disease and the immune trait from a genetic perspective still requires further confirmation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This study used two\u2010sample Mendelian randomization (MR) to assess causal relationship of immune cells with NMOSD. A total of 731 immune phenotyping traits were considered as exposure factors. NMOSD group is defined as outcome factor, which single\u2010nucleotide polymorphisms (SNPs) obtained from the study of Karol Estrada et\u00a0al. (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0215 NMOSD cases). The disease group was subcategorized into three groups based on the presence of AQP4\u2010IgG or not. We then enrolled 27 NMOSD patients and 17 healthy controls for peripheral blood flow cytometric analyses to validate part of our findings.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In this study, we found multiple possible genetic associations between immune cells and NMOSD. Beyond the well\u2010recognized roles of T and B cells, diverse myeloid\u2010lineage cells may also contribute to NMOSD pathophysiology. For AQP4\u2010IgG seropositive patient, myeloid cells, including dendritic cells (DCs) and the surface molecule CD80, granulocytic myeloid\u2010derived suppressor cells (MDSCs), and the molecule CX3CR1 may have a protective role in this group. In AQP4\u2010IgG seronegative patients, molecules like herpesvirus entry mediator (HVEM) exert pathogenic roles in NMOSD. Further flow\u2010cytometric analysis revealed that the proportion of MDSCs in NMOSD patients was lower, consistent with the MR analysis. However, the phenotypic expression of CX3CR1 in our NMOSD cohort yielded results opposite to those of the MR analysis. Additionally, many immune traits were correlated with the clinical phenotypes of NMOSD patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusio<\/jats:title>\n                    <jats:p>Adaptive immune cells play significant role in NMOSD patients.Certain innate immune cells (e.g., DCs and MDSCs) and surface molecules (e.g., CX3CR1 and CD80) may correlate with certain clinical phenotypes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.71400","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T06:39:50Z","timestamp":1776407990000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Causal Exposures of Immune Cells in Neuromyelitis Optica Spectrum Disorders: A Mendelian Randomization Study and Flow Cytometry Analysis"],"prefix":"10.1002","volume":"16","author":[{"given":"Jingru","family":"Ren","sequence":"first","affiliation":[{"name":"Department of Neurology Peking University First Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianchun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology Peking University First Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyu","family":"Niu","sequence":"additional","affiliation":[{"name":"Department of Neurology Peking University First Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Neurology Peking University First Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology Peking University First Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjun","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Neurology Peking University First Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Neurology Peking University First Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology Peking University First Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoxia","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology Peking University First Hospital  Beijing 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