Department of Medicine, University of California San Francisco, San Francisco, California, United States of America.
Cardiovascular Research Institute, University of California San Francisco, San Francisco, California, United States of America.
PLoS One. 2020 Oct 6;15(10):e0240319. doi: 10.1371/journal.pone.0240319. eCollection 2020.
Human mesenchymal stem/stromal cells (hMSCs) are a promising therapy for acute respiratory distress syndrome (ARDS) and other inflammatory conditions. While considerable research has focused on paracrine effects and mitochondrial transfer that improve lung fluid balance, hMSCs are well known to have immunomodulatory properties as well. Some of these immunomodulatory properties have been related to previously reported paracrine effectors such as indoleamine-2,3-dioxygenase (IDO), but these effects cannot fully account for cell-contact dependent immunomodulation. Here, we report that CD40 is upregulated on hMSCs under the same conditions previously reported to induce IDO. Further, CD40 transcription is also upregulated on hMSCs by ARDS pulmonary edema fluid but not by hydrostatic pulmonary edema fluid. Transcription of CD40, as well as paracrine effectors TSG6 and PTGS2 remained significantly upregulated for at least 12 hours after withdrawal of cytokine stimulation. Finally, induction of this immune phenotype altered the transdifferentiation of hMSCs, one of their hallmark properties. CD40 may play an important role in the immunomodulatory effects of hMSCs in ARDS and inflammation.
人骨髓间充质干细胞（hMSCs）是急性呼吸窘迫综合征（ARDS）和其他炎症疾病的有前途的治疗方法。虽然大量研究集中在改善肺液平衡的旁分泌作用和线粒体转移上，但 hMSCs 也具有免疫调节特性。这些免疫调节特性中的一些与先前报道的旁分泌效应物有关，如吲哚胺 2,3-双加氧酶（IDO），但这些效应不能完全解释细胞接触依赖性免疫调节。在这里，我们报告在先前报道诱导 IDO 的相同条件下，hMSCs 上的 CD40 上调。此外，ARDS 肺水肿液而不是静水肺水肿液也可上调 hMSCs 上的 CD40 转录。CD40 的转录以及旁分泌效应物 TSG6 和 PTGS2 的转录在细胞因子刺激停止后至少 12 小时仍显著上调。最后，这种免疫表型的诱导改变了 hMSCs 的转分化，这是其标志特性之一。CD40 可能在 hMSCs 在 ARDS 和炎症中的免疫调节作用中发挥重要作用。
