Rodriguez Stéphane, Couloume Laura, Ferrant Juliette, Vince Nicolas, Mandon Marion, Jean Rachel, Monvoisin Celine, Leonard Simon, Le Gallou Simon, Silva Nayane S B, Bourguiba-Hachemi Sonia, Laplaud David, Garcia Alexandra, Casey Romain, Zephir Helene, Kerbrat Anne, Edan Gilles, Lepage Emmanuelle, Thouvenot Eric, Ruet Aurelie, Mathey Guillaume, Gourraud Pierre-Antoine, Tarte Karin, Delaloy Celine, Amé Patricia, Roussel Mikael, Michel Laure
Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche U1236, Université Rennes, Etablissement Français du Sang Bretagne, LabEx IGO, Rennes, France.
Pole Biologie-Centre Hospitalier Universitaire (CHU) Rennes, Rennes, France.
Front Immunol. 2025 Jan 8;15:1494842. doi: 10.3389/fimmu.2024.1494842. eCollection 2024.
Myeloid cells trafficking from the periphery to the central nervous system are key players in multiple sclerosis (MS) through antigen presentation, cytokine secretion and repair processes.
Combination of mass cytometry on blood cells from 60 MS patients at diagnosis and 29 healthy controls, along with single cell RNA sequencing on paired blood and cerebrospinal fluid (CSF) samples from 5 MS patients were used for myeloid cells detailing.
Myeloid compartment study demonstrated an enrichment of a peculiar classical monocyte population in 22% of MS patients at the time of diagnosis. Notably, this patients' subgroup exhibited a more aggressive disease phenotype two years post-diagnosis. This monocytic population, detected in both the CSF and blood, was characterized by CD206, CD209, CCR5 and CCR2 expression, and was found to be more frequent in MS patients carrying the HLA-DRB1*15:01 allele. Furthermore, pathways analysis predicted that these cells had antigen presentation capabilities coupled with pro-inflammatory phenotype.
Altogether, these results point toward the amplification of a specific and pathogenic myeloid cell subset in MS patients with genetic susceptibilities.
从外周向中枢神经系统迁移的髓样细胞通过抗原呈递、细胞因子分泌和修复过程，在多发性硬化症（MS）中发挥关键作用。
对60例确诊的MS患者和29例健康对照者的血细胞进行质谱流式细胞术分析，并对5例MS患者的配对血液和脑脊液（CSF）样本进行单细胞RNA测序，以详细分析髓样细胞。
髓样细胞区室研究表明，在诊断时，22%的MS患者中存在一种特殊的经典单核细胞群富集。值得注意的是，该患者亚组在诊断后两年表现出更具侵袭性的疾病表型。在脑脊液和血液中均检测到的这种单核细胞群，其特征在于CD206、CD209、CCR5和CCR2的表达，并且在携带HLA-DRB1*15:01等位基因的MS患者中更为常见。此外，通路分析预测这些细胞具有抗原呈递能力以及促炎表型。
总之，这些结果表明在具有遗传易感性的MS患者中，特定的致病性髓样细胞亚群会扩增。
