Department of Biology, Tunis El Manar University, Tunis 1068, Tunisia.
Laboratory of Transmission, Control and Immunobiology of Infections, Institut Pasteur de Tunis, Tunis 1002, Tunisia.
Cells. 2022 Apr 12;11(8):1306. doi: 10.3390/cells11081306.
Remitting-RelapsingMultiple Sclerosis (RRMS) and Neuro-Behçet Disease (NBD) are two chronic neuroinflammatory disorders leading to neurological damage. Herein, we investigated in these patients the IL-10-producing cells during the early stages of these disorders. Cellular and molecular investigations were carried out on treatment naive patients suffering from RRMS and NBD recruited at the first episode of clinical relapse. Our findings demonstrate that CSF-B cells from NBD patients, but not RRMS, are the major source of intrathecal IL-10 as compared to T-CD4 cells. Moreover, we showed a lower expression of TGF-β and IL35, in the CSF cells of NBD patients as compared to the control group. Specific in vitro CpG stimulation of peripheral blood B cells from NBD patients resulted in a concomitant early mRNA expression of IL6 and IL10 but was limited to IL10 for RRMS patients. Furthermore, mRNA expression of IL-6 and IL-10 receptors was assessed and intriguingly IL6ST receptor subunit was significantly lower in NBD CSF, but not RRMS while IL10RB was increased in both. Deciphering the role of increased IL-10-producing B cells and IL10RB despite relapsing disease as well as the discordant expression of IL6 and IL6ST may pave the way for a better understanding of the pathophysiology of these neuro-inflammatory disorders.
缓解-复发多发性硬化症 (RRMS) 和神经白塞病 (NBD) 是两种导致神经损伤的慢性神经炎症性疾病。在此,我们研究了这些疾病早期患者的 IL-10 产生细胞。对首次临床复发时招募的 RRMS 和 NBD 初治患者进行细胞和分子研究。与 T-CD4 细胞相比,我们的研究结果表明,NBD 患者的 CSF-B 细胞而非 RRMS 患者的 CSF-B 细胞是鞘内 IL-10 的主要来源。此外,与对照组相比,NBD 患者的 CSF 细胞中 TGF-β 和 IL35 的表达较低。与 RRMS 患者相比,NBD 患者外周血 B 细胞经 CpG 特异性体外刺激后,早期同时表达 IL6 和 IL10,但仅限于 IL10。此外,评估了 IL-6 和 IL-10 受体的 mRNA 表达,令人惊讶的是,NBD CSF 中的 IL6ST 受体亚基显著降低,而 RRMS 则增加,而 IL10RB 在两者中均增加。尽管疾病复发,但增加的产生 IL-10 的 B 细胞和 IL10RB 的作用以及 IL6 和 IL6ST 的表达不一致,可能为更好地理解这些神经炎症性疾病的病理生理学铺平道路。