Stromal cells from perinatal and adult sources modulate the inflammatory immune response in vitro by decreasing Th1 cell proliferation and cytokine secretion
Stromal cells from perinatal and adult sources modulate the inflammatory immune response in vitro by decreasing Th1 cell proliferation and cytokine secretion
复制标题
DOI：
10.1002/sctm.19-0123
复制
发表时间：
2019-10-22
影响因子：
6
通讯作者：
Murphy, Sean, V
中科院分区：
文献类型：
--
作者：
Khoury, Oula;Atala, Anthony;Murphy, Sean, V
许多免疫介导的疾病与 Th1 反应失调失衡有关，导致疾病的发作、严重程度和损害。许多疗法，例如免疫调节剂或抗 TNF-α 抗体，通常无法预防疾病进展和改善疾病状况。因此，针对炎症环境的新疗法将对预防炎症性疾病的进展产生重大影响。我们研究了源自羊水 (AFSC)、胎盘 (PLSC) 和骨髓源间充质基质细胞 (BM-MSC) 的人基质细胞在调节体外刺激的循环血液源性免疫细胞的炎症反应中的作用。从健康个体的血液中分离出免疫细胞，并在体外用抗原刺激以激活对刺激的炎症反应。 AFSC、BM-MSC 和 PLSC 与受刺激的白细胞、中性粒细胞或淋巴细胞共培养。评估了炎症细胞因子的产生、中性粒细胞迁移、酶脱颗粒、T 细胞增殖和亚群。所有三种基质细胞类型的共培养均降低了脂多糖刺激的白细胞中炎性细胞因子和酶的基因表达，例如IL-1β、IFN-γ、TNF-α、中性粒细胞弹性蛋白酶和转录因子NF-κB。对于分离的植物血凝素刺激的外周血单核细胞，细胞共培养会导致淋巴细胞增殖减少。这种效应与 Th1 淋巴细胞数量减少和 IFN-γ 分泌水平降低相关。干细胞转化医学2019
Many immune-mediated conditions are associated with a dysregulated imbalance toward a Th1 response leading to disease onset, severity, and damage. Many of the therapies such as immunomodulators or anti-TNF-alpha antibodies often fall short in preventing disease progression and ameliorating disease conditions. Thus, new therapies that can target inflammatory environments would have a major impact in preventing the progression of inflammatory diseases. We investigated the role of human stromal cells derived from the amniotic fluid (AFSCs), the placenta (PLSCs), and bone marrow-derived mesenchymal stromal cells (BM-MSCs) in modulating the inflammatory response of in vitro-stimulated circulating blood-derived immune cells. Immune cells were isolated from the blood of healthy individuals and stimulated in vitro with antigens to activate inflammatory responses to stimuli. AFSC, BM-MSCs, and PLSCs were cocultured with stimulated leukocytes, neutrophils, or lymphocytes. Inflammatory cytokine production, neutrophil migration, enzymatic degranulation, T cell proliferation, and subsets were evaluated. Coculture of all three stromal cell types decreased the gene expression of inflammatory cytokines and enzymes such as IL-1 beta, IFN-gamma, TNF-alpha, neutrophil elastase, and the transcription factor NF-kappa B in lipopolysaccharide-stimulated leukocytes. With isolated phytohemagglutinin-stimulated peripheral blood mononuclear cells, cells coculture leads to a decrease in lymphocyte proliferation. This effect correlated with decreased numbers of Th1 lymphocytes and decreased secreted levels of IFN-gamma. Stem Cells Translational Medicine2019