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Tonsil-derived mesenchymal stromal cells produce CXCR2-binding chemokines and acquire follicular dendritic cell-like phenotypes under TLR3 stimulation

机译:扁桃体来源的间充质基质细胞产生CXCR2结合趋化因子,并在TLR3刺激下获得卵泡树突状细胞样表型。

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We previously isolated mesenchymal stromal cells from human tonsils (T-MSCs) and showed the potential of these cells to differentiate into the mesodermal lineage and acquire a follicular dendritic cell (FDC) phenotype under cytokine stimulation. Because these T-MSCs were originally isolated from inflamed tonsillar tissues, we were curious about their activation status in response to innate immune stimuli, such as Toll-like receptors (TLRs). Therefore, we analyzed the expression profile of TLRs in T-MSCs and stimulated the T-MSCs with TLR agonists. TLR3 stimuli induced C-C chemokine receptor type 6 expression in T-MSCs after 24 h. Furthermore, results from cytokine arrays showed increases in epithelial neutrophil-activating peptide-78/C-X-C motif chemokine (CXCL) 5, granulocyte chemotactic protein-2/CXCL6, growth-related oncogene-alpha/CXCL1, interleukin-8/CXCL8, and interferon gamma-induced protein-10/CXCL10. CD54 expression was also increased after TLR3 stimulation. However, co-culturing T-MSCs with human B cells did not induce B-cell proliferation. This suggests that TLR3 stimulates the differentiation of T-MSCs into FDC-like cells and induces chemokine secretion, possibly by recruiting C-X-C chemokine receptor 2-expressing immune cells. In addition, T-MSCs also appeared to exert immunomodulatory effects by inhibiting B-cell proliferation, possibly by down-regulating CD18. (C) 2015 Elsevier Ltd. All rights reserved.
机译:我们先前从人扁桃体(T-MSC)分离了间充质基质细胞,并显示了这些细胞分化为中胚层谱系并在细胞因子刺激下获得滤泡树突状细胞(FDC)表型的潜力。因为这些T-MSC最初是从发炎的扁桃体组织中分离出来的,所以我们对它们响应先天性免疫刺激(例如Toll样受体(TLR))的激活状态感到好奇。因此,我们分析了TLR在T-MSC中的表达谱,并用TLR激动剂刺激了T-MSC。 24小时后,TLR3刺激诱导T-MSC中C-C趋化因子受体6型表达。此外,细胞因子阵列的结果显示上皮中性粒细胞激活肽-78 / CXC基序趋化因子(CXCL)5,粒细胞趋化蛋白-2 / CXCL6,生长相关癌基因α/ CXCL1,白介素-8 / CXCL8和干扰素增加。 γ诱导蛋白10 / CXCL10。 TLR3刺激后,CD54表达也增加。然而,将T-MSC与人B细胞共培养不会诱导B细胞增殖。这表明TLR3可能通过募集表达C-X-C趋化因子受体2的免疫细胞来刺激T-MSC分化为FDC样细胞并诱导趋化因子分泌。此外,T-MSC似乎还通过抑制B细胞增殖(可能通过下调CD18来发挥免疫调节作用)。 (C)2015 Elsevier Ltd.保留所有权利。

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