Instituto de Biomedicina de Sevilla, IBiS (Universidad de Sevilla, HUVR, Junta de Andalucía, CSIC), Seville, Spain.
Departamento de Bioquímica Médica y Biología Molecular e Inmunología, Universidad de Sevilla, Seville, Spain.
Sci Rep. 2019 Feb 19;9(1):2302. doi: 10.1038/s41598-019-38897-w.
CD39, an ectonucleotidase that hydrolyses pro-inflammatory ATP, is a marker of highly active and suppressive T regulatory cells (Tregs). Although CD39 has a role in Treg suppression and might be important in the control of neuroinflammation in relapsing-remitting multiple sclerosis (RR-MS), to date, there are contradictory reports concerning the Tregs expression of CD39 in RR-MS patients. Thus, our objectives were to assess the activity and expression of CD39, especially in Tregs from peripheral blood mononuclear cells (PBMCs) of relapsing RR-MS patients compared with control subjects and to evaluate the association of CD39+ Tregs with disability and the odds of RR-MS. The activity and expression of CD39 and the CD39 Treg frequency were measured in PBMCs from 55 relapsing RR-MS patients (19 untreated and 36 receiving immunomodulatory treatment) and 55 age- and sex-paired controls. Moreover, the association between CD39 Tregs and RR-MS was assessed by multivariate logistic regression. CD39 activity and the frequency of CD39-expressing Tregs were elevated in relapsing RR-MS patients. Moreover, CD39 Tregs were significantly correlated with the EDSS score and were independently associated with the odds of RR-MS. Our results highlight the relevance of CD39 Treg subset in the clinical outcomes of RR-MS.
CD39 是一种水解促炎 ATP 的细胞外核苷酸酶,是高活性和抑制性调节性 T 细胞(Tregs)的标志物。虽然 CD39 在 Treg 抑制中起作用,并且可能在复发缓解型多发性硬化症(RR-MS)的神经炎症控制中很重要,但迄今为止,关于 RR-MS 患者 Tregs 中 CD39 的表达存在相互矛盾的报道。因此,我们的目的是评估 CD39 的活性和表达,特别是在外周血单个核细胞(PBMCs)中从 RR-MS 患者的 Tregs 与对照组相比,并评估 CD39+Tregs 与残疾和 RR-MS 的几率之间的关联。我们在 55 名 RR-MS 复发患者(19 名未治疗和 36 名接受免疫调节治疗)和 55 名年龄和性别配对的对照组的 PBMCs 中测量了 CD39 的活性和表达,以及 CD39 Treg 的频率。此外,我们通过多元逻辑回归评估了 CD39 Tregs 与 RR-MS 之间的关联。RR-MS 患者的 CD39 活性和表达 CD39 的 Tregs 频率升高。此外,CD39 Tregs 与 EDSS 评分显著相关,并且与 RR-MS 的几率独立相关。我们的结果强调了 CD39 Treg 亚群在 RR-MS 临床结果中的相关性。