SLE患者B细胞自噬水平显著增强与IFN-I通路活化密切相关。我们前期发现正常MSC能够通过分泌PGE2调控B细胞中IFN-I通路的活化，但狼疮的MSC免疫调控能力缺陷；SLE患者骨髓来源MSC中lncRNA HULC显著高表达，异常表达的lncRNA HULC不仅能够促进MSC自噬抑制其分泌PGE2，还能直接上调B细胞中IFN-I通路关键分子JAK1的表达。可是迄今MSC的lncRNA HULC如何调控B细胞的IFN-I通路的活化及自噬还不清楚。我们推测SLE病程中lncRNA HULC可通过促进MSC自噬抑制其分泌PGE2和促进B细胞中JAK1表达这两种途径，共同调控B细胞中IFN-I通路活化及自噬。本研究将探索MSC通过lncRNA HULC调控B细胞自噬的机制，以便提出MSC调控B细胞自噬在SLE发病中的新理论，也期望为MSC移植临床应用于SLE治疗提供新依据。

Enhanced autophagy and the activation of type I interferon (IFN-I) pathway in B cells have been identified to participate in the progression of patients with systemic lupus erythematosus (SLE). Our previous study found IFN-I could activate the autophagy in B cells from human peripheral blood mononuclear cells (PBMCs) and mice spleen, which implicated that autophagy in B cells was remarkably associated with the activation of type I interferon (IFN-I) pathway in SLE patients. Importantly, the transplantation of normal mesenchymal stem cells (MSCs) was demonstrated to alleviate the symptoms of SLE. We had found that normal MSCs could negatively control the IFN-I pathway of B cells via prostaglandin E2 (PGE2), but MSCs from SLE failed in this manipulation with unclear mechanisms. Emerging evidence showed that the long non-coding RNAs (lncRNA), a recently discovered class of non-coding genes, are an abundant and diverse class of gene regulators. Dysfunction of lncRNAs was one of risk factors for the development of SLE. We noted that the level of lncRNA HULC and autophagy-related genes was highly elevated in MSCs of SLE patients. Besides, highly up-regulated expression of lncRNA HULC was observed to activate the autophagy of MSCs in vitro and abrogate the secretion of PGE2 which resulted in restoring the IFN-I pathway in B cells. Interestingly, lncRNA HULC was noted to be secreted by MSCs and the lncRNA HULC was reported to down-regulated the microRNA-372 which directly targeted JAK1, the key adapter of the IFN-I pathway, to amplify the the IFN-I pathway in B cells, leading to the activation of autophagy in B cells and then the aggravation of SLE. However, on the one hand, the mechanism of lncRNA HULC to control the autophagy and the secretion of PGE2 of MSCs were unclear for now. On another hand, there had no evidences that MSCs could directly secret lncRNA HULC to target the IFN-I pathway and subsequently enhanced autophagy in B cells. Therefore, we speculate that the enhanced autophagy in B cells could be induced by the lncRNA HULC/PGE2 signal by the autophagy of MSCs and, alternatively, the lncRNA HULC/JAK1 signal of B cells. In summary, this study would shed light on the mechanism of enhanced autophagy in B cell by MSCs via the aberrant expression of lncRNA HULC, which contribute to propose a new theory that MSCs regulate the autophagy in B cells during the development of SLE. Furthermore, as the essential regulator in MSCs, targeting lncRNA HULC would also help us to improve the efficiency of MSCs transplantation for the treatment of SLE patients in clincal.