He Haiping, Yang Tonghua, Li Fan, Zhang Lihua, Ling Xiaosui
Department of Hematology, The First People's Hospital of Yunnan Province, Kunming, China; Yunnan Blood Disease Clinical Medical Center, Kunming, China; Yunnan Blood Disease Hospital, Kunming, China; Kunming University of Science and Technology, Kunming, China.
Department of Hematology, The First People's Hospital of Yunnan Province, Kunming, China; Yunnan Blood Disease Clinical Medical Center, Kunming, China; Yunnan Blood Disease Hospital, Kunming, China.
Int Immunopharmacol. 2021 Nov;100:108054. doi: 10.1016/j.intimp.2021.108054. Epub 2021 Sep 3.
Allogeneic hematopoietic stem cell transplantation (HSCT) remains the key for the treatment of malignant hematological diseases, and acute graft-versus-host disease (aGVHD) that might occur after allogenic transplantation can be life threatening and promote disease recurrence. GVHD damages the various parts of the body by upregulating T helper 1 cytokines (Th1) cytokines and stimulating CD4、CD8 + T cells. GVHD can exhibit significant immunoregulatory effects, but could be easily affected by the mesenchymal stem cells (MSC) environment, and hence the MSC immunosuppressive effects on GVHD remain unpredictable. Hence, to better understand the role of MSC in the prevention and treatment of GVHD, umbilical cord derived mesenchymal stem cells (UC-MSC) were pre-treated with Chinese medicine Asarinin and IFN-γ. In the mix lymphocyte reaction, we found that Asarinin pre-treated UC-MSC can exert significantly greater inhibition towards the proliferation of CD4 and CD8 + T cells, down-regulate Th1 type cytokines, up-regulate Th2 type cytokines, and reduce the inflammatory damage to liver, lung and intestine of aGVHD mice model. Moreover, Asarinin can cooperate with IFN-γto promote UC-MSC to secrete indoleamine 2,3-dioxygenase (IDO). Our findings establish that Asarinin pre-treated UC-MSC can significantly promote the immunosuppressive effects of MSC on aGVHD after hematopoietic stem cell transplantation.
异基因造血干细胞移植(HSCT)仍然是治疗恶性血液病的关键,而异基因移植后可能发生的急性移植物抗宿主病(aGVHD)可能危及生命并促进疾病复发。移植物抗宿主病通过上调辅助性T细胞1(Th1)细胞因子并刺激CD4、CD8 + T细胞来损害身体的各个部位。移植物抗宿主病可表现出显著的免疫调节作用,但很容易受到间充质干细胞(MSC)环境的影响,因此MSC对移植物抗宿主病的免疫抑制作用仍然不可预测。因此,为了更好地了解MSC在预防和治疗移植物抗宿主病中的作用,脐带间充质干细胞(UC-MSC)用中药细辛脂素和干扰素-γ进行了预处理。在混合淋巴细胞反应中,我们发现细辛脂素预处理的UC-MSC对CD4和CD8 + T细胞的增殖具有显著更强的抑制作用,下调Th1型细胞因子,上调Th2型细胞因子,并减少aGVHD小鼠模型肝脏、肺和肠道的炎症损伤。此外,细辛脂素可与干扰素-γ协同作用,促进UC-MSC分泌吲哚胺2,3-双加氧酶(IDO)。我们的研究结果表明,细辛脂素预处理的UC-MSC可显著促进MSC对造血干细胞移植后aGVHD的免疫抑制作用。