探討間質幹細胞對自體免疫疾病病人之T細胞的免疫調控能力及其機制

Abstract

自體免疫疾病是一種慢性發炎的疾病，且第一型輔助性T細胞與第十七型輔助性T細胞在其致病機轉中扮演不可或缺的角色。間質幹細胞具有免疫抑制的功能，並且被廣泛地研究作為許多自體免疫疾病療法的可能性。在本篇論文中，我們研究分離自新來源的胎盤絨毛膜褪膜間質幹細胞(pcMSC)是否具有抑制自體免疫疾病病人之T細胞功能的能力。我們也進一步探討pcMSC免疫調控能力的機轉，並研究IL-33是否在其中扮演一定的角色。我們發現pcMSC無法抑制小兒自體免疫疾病病人之T細胞。重要的是，pcMSC可以顯著地抑制多發性硬化症與視神經脊髓炎病人之完全活化的T細胞，不過它也意外地對低度活化之T細胞表現免疫促進的效果。我們更進一步證明pcMSC的促進效果不須依靠細胞之間的接觸，且經IFN-前處理後亦無法避免此現象的發生。再者，pcMSC的抑制與促進能力皆與IL-33無關。總結來說，pcMSC具有治療多發性硬化症與視神經脊髓炎的潛能，但其免疫促進的效果必須被審慎評估。

Autoimmune disease is a type of chronic inflammatory disease, and T helper 1 (Th1) and T helper 17 (Th17) cells play a crucial role in its pathogenesis. Mesenchymal stem cells (MSC) possess immunosuppressive function and are widely studied as a potential cell therapy to many autoimmune diseases. Here, we investigated the therapeutic potential of the newly isolated placenta choriodecidual membrane-derived MSCs (pcMSCs) on T cell function of various autoimmune diseases. We also investigated the mechanisms of the immune-modulatory effects of pcMSCs, and evaluated whether IL-33 plays a role in them. We found that pcMSCs could not inhibit the T cells derived from pediatric autoimmune patients. Of note, pcMSCs significantly suppressed high-reactive T cells from adult multiple sclerosis (MS) and neuromyelitis optica (NMO) patients, although they displayed an unexpected enhancing effect on low-reactive T cells. We further demonstrated that the enhancing effect of pcMSCs is not dependent of cell-cell contact, and may not be prevented by IFN- pretreatment. Also, the suppressive and promoting function of pcMSCs were not mediated by IL-33. In conclusion, pcMSCs may have the potential to remedy MS and NMO, but their immune-enhancing effect should be carefully considered beforehand.