Cha Lilian, Jones Anderson P, Trend Stephanie, Byrne Scott N, Fabis-Pedrini Marzena J, Carroll William M, Lucas Robyn M, Cole Judith M, Booth David R, Kermode Allan G, Hart Prue H
Telethon Kids Institute University of Western Australia Perth WA Australia.
Faculty of Medicine and Health Westmead Institute for Medical Research University of Sydney Westmead NSW Australia.
Clin Transl Immunology. 2018 Aug 16;7(8):e1037. doi: 10.1002/cti2.1037. eCollection 2018.
Clinically isolated syndrome (CIS) is the earliest clinical episode in multiple sclerosis (MS). A study of circulating cells from patients with CIS may help us understand the transition to, and processes associated with, the development of MS.
As immune cell activity can be determined by flux through metabolic pathways, the mRNA expression of l-tryptophan- and l-arginine-catabolising enzymes, indoleamine 2,3-dioxygenase (IDO) 1 and IDO2 and arginase (ARG) 1 and ARG2, respectively, was compared between peripheral blood mononuclear cells (PBMCs) from healthy controls, and patients with CIS and definite MS. As one measure of cell function, cytokine mRNA levels were analysed directly and in cells after culture for 4 h in the absence of regulatory factors in autologous serum.
When measured directly , the expression of IDO and ARG was greater in cells from patients with CIS and MS than cells from healthy controls. Although not linked to IDO and ARG expression, PBMCs from the CIS patients were characterised by low IL-10 and TGFB mRNA levels and not by greater expression of proinflammatory cytokines. When the cells were cultured for 4 h without autologous serum, pro- and anti-inflammatory cytokine mRNA levels positively correlated with IDO1 expression, and TGFB mRNA levels correlated with ARG1 expression.
Higher IDO and ARG expression in CIS and MS provides one sustained homeostatic mechanism to control MS-associated inflammation. However, potent extrinsic mediators in serum may regulate immune cell function in CIS and associations between IDO, ARG and cytokine expression.
临床孤立综合征（CIS）是多发性硬化症（MS）最早出现的临床发作。对CIS患者循环细胞的研究可能有助于我们了解向MS转变的过程以及与之相关的进程。
由于免疫细胞活性可通过代谢途径的通量来确定，因此分别比较了健康对照者、CIS患者和确诊MS患者外周血单个核细胞（PBMC）中色氨酸和精氨酸分解代谢酶（分别为吲哚胺2,3-双加氧酶（IDO）1和IDO2以及精氨酸酶（ARG）1和ARG2）的mRNA表达。作为细胞功能的一项指标，直接分析细胞因子mRNA水平，并在无自体血清中调节因子的情况下培养4小时后的细胞中进行分析。
直接测量时，CIS和MS患者细胞中IDO和ARG的表达高于健康对照者的细胞。虽然与IDO和ARG表达无关，但CIS患者的PBMC具有低IL-10和TGFB mRNA水平的特征，而非促炎细胞因子表达增加。当细胞在无自体血清的情况下培养4小时时，促炎和抗炎细胞因子mRNA水平与IDO1表达呈正相关，TGFB mRNA水平与ARG1表达相关。
CIS和MS中较高的IDO和ARG表达提供了一种持续的稳态机制来控制与MS相关的炎症。然而，血清中强大的外在介质可能调节CIS中的免疫细胞功能以及IDO、ARG与细胞因子表达之间的关联。
