Bahrini Khadija, Belghith Meriam, Maghrebi Olfa, Bekir Jihène, Kchaou Mariem, Jeridi Cyrine, Amouri Rim, Hentati Faycel, Belal Samir, Ben Sassi Samia, Barbouche Mohamed-Ridha
Institut Pasteur de Tunis, LTCII, LR11IPT02, Tunis 1002, Tunisia; Tunis El Manar University, Tunis 1068, Tunisia.
Neurological Department of Charles Nicolle Hospital, Tunis, Tunisia.
Cytokine. 2020 Mar 6;130:155054. doi: 10.1016/j.cyto.2020.155054.
Treg-mediated immune suppression involves many molecular mechanisms including the cleavage of inflammatory extracellular ATP to adenosine by CD39 ectoenzyme. In the peripheral blood of Multiple Sclerosis (MS) patients, it has been suggested that CD39+ Treg cells have the potential to suppress pro-inflammatory IL-17 secreting cells. Herein, we studied cellular phenotype and mRNA expression of CD39 and CD73 ectoenzymes in the Cerebrospinal fluid (CSF) of MS patients and another neuro-inflammatory disease: the Neuro-behçet's disease (NBD). Using qRT-PCR, we assessed mRNA expression of CD39 and CD73 as well as anti-inflammatory (IL-10) and pro-inflammatory (IL-6, TNF-α, IL-1β) cytokines in patients Peripheral blood mononuclear cells (PBMCs) and CSF of 28 relapsing-remitting multiple sclerosis (RRMS), 20 NBD and 22 controls with non inflammatory neurological disorders (NIND). The most substantial result in the CSF was the higher expression of CD39 in both RRMS and NBD patients compared to NIND. While, the expression of CD73 in CSF samples of NBD was low. In RRMS samples, we detected a significant positive correlation of both CD39 and CD73 with IL-10 expression. Moreover, results by flow cytometry revealed a high percentage of CD39 Treg cells in RRMS CSF. CD39 was preferentially expressed on B cells of NBD. Regarding inflammatory response, we showed a significant increase of IL-6 mRNA expression in NBD patients CSF while in RRMS this increase concerned TNF-α. These results bring evidence that CD39 correlates positively with an anti-inflammatory IL-10 response in RRMS. In contrast, no such association was observed in CSF of NBD patients and CD39 was preferentially expressed on B cells.
调节性T细胞（Treg）介导的免疫抑制涉及许多分子机制，包括通过CD39外切酶将炎性细胞外ATP裂解为腺苷。在多发性硬化症（MS）患者的外周血中，有人提出CD39 + Treg细胞具有抑制促炎性白细胞介素-17分泌细胞的潜力。在此，我们研究了MS患者和另一种神经炎性疾病：神经白塞病（NBD）患者脑脊液（CSF）中CD39和CD73外切酶的细胞表型和mRNA表达。我们使用定量逆转录聚合酶链反应（qRT-PCR）评估了28例复发缓解型多发性硬化症（RRMS）、20例NBD和22例非炎性神经系统疾病（NIND）对照患者外周血单个核细胞（PBMC）和脑脊液中CD39和CD73以及抗炎（白细胞介素-10）和促炎（白细胞介素-6、肿瘤坏死因子-α、白细胞介素-1β）细胞因子的mRNA表达。脑脊液中最显著的结果是，与NIND相比，RRMS和NBD患者中CD39的表达均较高。而NBD患者脑脊液样本中CD73的表达较低。在RRMS样本中，我们检测到CD39和CD73与白细胞介素-10表达均呈显著正相关。此外，流式细胞术结果显示RRMS脑脊液中CD39 + Treg细胞的比例很高。CD39在NBD的B细胞上优先表达。关于炎症反应，我们发现NBD患者脑脊液中白细胞介素-6 mRNA表达显著增加，而在RRMS中，这种增加与肿瘤坏死因子-α有关。这些结果证明，在RRMS中CD39与抗炎性白细胞介素-10反应呈正相关。相比之下，在NBD患者的脑脊液中未观察到这种关联，且CD39在B细胞上优先表达。
