{
  "abstract": "Multiple sclerosis (MS) is a complex inflammatory disease of the CNS resulting from an intricate interplay between genetic predisposition and environmental factors. Vitamin D (VD) deficiency is one of the established risk factors for MS. CD46 costimulation of CD4+ T cells induces a switch from Th1 to type I regulatory cells (Tr1), characterized by increased IL-10 production. This switch is impaired in MS T cells but can be restored by VD, which also strongly promotes expression of CD226 on CD46-activated T cells. The rs763361 polymorphism in the CD226 gene, resulting in a nonsynonymous Gly307Ser variant, is associated with increased risk for MS. Herein, we show that expression of this CD226 risk allele disrupts the ability of CD46-activated T cells to operate the IFN-γ/IL-10 switch upon VD exposure. Mechanistically, the risk variant impairs activation of the integrin LFA-1, which promotes the Tr1 phenotype. LFA-1-mediated Tr1 differentiation is also impaired in MS T cells expressing the CD226 risk allele upon CD46 and VD stimulation. Our study unveils how, in the context of MS susceptibility, a genetic polymorphism and an environmental factor act in concert to control the differentiation of Tr1 cells.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 19,
  "authors": [
    {
      "name": "Saniya Kari"
    },
    {
      "name": "Aymeline Debonlier"
    },
    {
      "name": "Thibault Angles"
    },
    {
      "name": "Beatriz Chaves"
    },
    {
      "name": "Charles Grosjean"
    },
    {
      "name": "Florence Bucciarelli"
    },
    {
      "name": "Valérie Duplan-Eche"
    },
    {
      "name": "Lucie Nozeran"
    },
    {
      "name": "Jessica Lavery"
    },
    {
      "name": "Elena Morandi"
    },
    {
      "name": "Beatrice Pignolet"
    },
    {
      "name": "Max Mimpen"
    },
    {
      "name": "Joost Smolders"
    },
    {
      "name": "Roland Liblau"
    },
    {
      "name": "Abdelhadi Saoudi"
    },
    {
      "name": "Jan Damoiseaux"
    },
    {
      "name": "Frederick Masson"
    },
    {
      "name": "Loïc Dupré"
    },
    {
      "name": "Anne Laurence Astier"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/20cvt450wefyd.bib",
  "cited_by": 0,
  "doi": "10.1172/jci202193",
  "fulltext_url": null,
  "id": "20cvt450wefyd",
  "issns": [
    "1558-8238"
  ],
  "landing_url": "https://hal.science/hal-05752803v1",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "hal",
      "1.sdv.imm"
    ],
    [
      "openalex",
      "2734|Multiple Sclerosis Research Studies"
    ]
  ],
  "openalex": "W7204907058",
  "pdf_url": "http://www.jci.org/articles/view/202193/files/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-01",
  "publisher": "American Society for Clinical Investigation",
  "ris": "https://research.draconitic.com/paper/20cvt450wefyd.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:35Z",
      "native_id": "hal-05752803",
      "source": "hal",
      "url": "https://hal.science/hal-05752803v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "hal:1.sdv.imm",
      "subfield": "immunology"
    }
  ],
  "title": "Multiple sclerosis-associated CD226 variant disrupts vitamin D-induced type I Treg differentiation by impairing LFA-1 activation",
  "title_text": "Multiple sclerosis-associated CD226 variant disrupts vitamin D-induced type I Treg differentiation by impairing LFA-1 activation",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:35Z",
  "url": "https://research.draconitic.com/paper/20cvt450wefyd",
  "venue": "The Journal of clinical investigation",
  "versions": []
}