Zhang Xin, Tao Yazhong, Chopra Manisha, Dujmovic-Basuroski Irena, Jin Jianping, Tang Yunan, Drulovic Jelena, Markovic-Plese Silva
Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
Department of Neurology, Clinical Center Serbia, Belgrade 11129, Serbia;
J Immunol. 2015 Jun 1;194(11):5139-49. doi: 10.4049/jimmunol.1401680. Epub 2015 Apr 20.
Clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS) is the earliest clinically evident phase of the disease, which may provide valuable insight into the molecular mechanisms of the initiation of the autoimmune response in MS. Our results introduce IL-11 as a new cytokine that plays a role in the autoimmune response in the early phase of the disease. IL-11 is the highest upregulated cytokine in the sera and cerebrospinal fluid from CIS patients, which is also increased in patients with clinically definitive relapsing-remitting MS in comparison with healthy control subjects. Serum IL-11 levels are significantly increased during clinical exacerbations in comparison with remissions in the same patients. CD4(+) cells represent a predominant cell source of IL-11 in the peripheral circulation, and the percentage of IL-11(+)CD4(+) cells is significantly increased in CIS patients in comparison with healthy control subjects. Furthermore, we have identified IL-11 as a new Th17-promoting cytokine, because it induces a differentiation of naive CD4(+) T cells into Th17 cells, as well as expansion of Th17 memory cells. Because the Th17 cytokines IL-17F, IL-21 and TNF-α, and TGF-β induce differentiation of naive cells in the IL-11-secreting CD4(+) cells, we propose that cross-talk between IL-11(+)CD4(+) and Th17 cells may play a role in the inflammatory response in relapsing-remitting MS.
提示多发性硬化症（MS）的临床孤立综合征（CIS）是该疾病最早出现临床症状的阶段，这可能为深入了解MS自身免疫反应启动的分子机制提供有价值的线索。我们的研究结果表明，白细胞介素-11（IL-11）是一种在疾病早期自身免疫反应中发挥作用的新细胞因子。IL-11是CIS患者血清和脑脊液中上调最为明显的细胞因子，与健康对照相比，临床确诊的复发缓解型MS患者体内该因子水平也有所升高。同一患者在临床病情加重期血清IL-11水平相比病情缓解期显著升高。CD4(+)细胞是外周循环中IL-11的主要细胞来源，与健康对照相比，CIS患者中IL-11(+)CD4(+)细胞的百分比显著增加。此外，我们已确定IL-11是一种新的促进Th17细胞分化的细胞因子，因为它可诱导初始CD4(+) T细胞分化为Th17细胞，并促使Th17记忆细胞扩增。由于Th17细胞因子IL-17F、IL-21和TNF-α以及转化生长因子-β（TGF-β）可诱导分泌IL-11的CD4(+)细胞中初始细胞的分化，我们推测IL-11(+)CD4(+)细胞与Th17细胞之间的相互作用可能在复发缓解型MS的炎症反应中发挥作用。
