Neuroimmunology Laboratory, Department of Neurology, Tel Aviv Sourasky Medical Center, Tel Aviv University, Tel Aviv, Israel.
J Neuroimmunol. 2011 Sep 15;238(1-2):96-103. doi: 10.1016/j.jneuroim.2011.08.003. Epub 2011 Aug 31.
One of the mechanisms known to play a key role in neuronal and oligodendroglial fate specification of neural stem cells (NSCs) is restriction of bone morphogenic proteins (BMP) signaling by BMP antagonists. Here, we demonstrate that follistatin mRNA and protein secreted levels in peripheral blood mononuclear cells (PBMCs) of relapsing-remitting multiple sclerosis (RR-MS) patients are significantly reduced compared to healthy controls (HC). We also observed a different profile of regulation mechanisms. Follistatin was similarly expressed and secreted by T lymphocytes and monocytes among the PBMCs of HC, and follistatin upregulation of HC was subjected to stimulation with both LPS and TNF-α. Among PBMCs of RR-MS patients, however, follistatin was found to be downregulated in their monocytes and unresponsive to stimulation with either LPS or TNF-α. Our results may shed some light on the mechanisms involved in remyelination failure in MS, which may be related to the inability of RR-MS patients' immune cells to provide a sufficient pro-neurogenic and oligodendrogenic niche, by expressing and secreting follistatin, in addition to the previously described noggin reduced expression. Our results indicate that the low expression of follistatin in immune cells of patients with RR-MS is a result of the altered immunoregulation of monocytes in these patients.
已知在神经干细胞（NSCs）的神经元和少突胶质细胞命运特化中起关键作用的机制之一是骨形态发生蛋白（BMP）拮抗剂对 BMP 信号的限制。在这里，我们证明与健康对照者（HC）相比，复发缓解型多发性硬化症（RR-MS）患者外周血单核细胞（PBMC）中的卵泡抑素 mRNA 和蛋白分泌水平显著降低。我们还观察到了不同的调节机制。在 HC 的 PBMC 中，卵泡抑素在 T 淋巴细胞和单核细胞中表达和分泌相似，HC 的卵泡抑素上调受到 LPS 和 TNF-α 的刺激。然而，在 RR-MS 患者的 PBMC 中，发现其单核细胞中的卵泡抑素下调，并且对 LPS 或 TNF-α的刺激均无反应。我们的结果可能阐明了 MS 中髓鞘再生失败的机制，这可能与 RR-MS 患者的免疫细胞无法通过表达和分泌卵泡抑素来提供足够的促神经发生和少突胶质细胞龛有关，除了先前描述的 Noggin 表达降低。我们的结果表明，RR-MS 患者免疫细胞中卵泡抑素的低表达是这些患者单核细胞免疫调节改变的结果。
