Chatterjee Arunima, Gogolak Péter, Blottière Hervé M, Rajnavölgyi Éva
Department of Immunology, Medical Faculty, University of Debrecen, Debrecen 4032, Hungary ; INRA, Unité de Virologie et Immunologie Moléculaires, Jouy-en-Josas, France ; AgroParisTech, Jouy-en-Josas, France.
Department of Immunology, Medical Faculty, University of Debrecen, Debrecen 4032, Hungary.
Mediators Inflamm. 2015;2015:579830. doi: 10.1155/2015/579830. Epub 2015 Apr 7.
Vitamin A plays an essential role in the maintenance of gut homeostasis but its interplay with chemokines has not been explored so far. Using an in vitro model system we studied the effects of human colonic epithelial cells (Caco2, HT-29, and HCT116) derived inflammatory stimuli on monocyte-derived dendritic cells and macrophages. Unstimulated Caco2 and HT-29 cells secreted CCL19, CCL21, and CCL22 chemokines, which could attract dendritic cells and macrophages and induced CCR7 receptor up-regulation by retinoic-acid resulting in dendritic cell migration. The chemokines Mk, CXCL16, and CXCL7 were secreted by all the 3 cell lines tested, and upon stimulation by IL-1β or TNF-α this effect was inhibited by ATRA but had no impact on CXCL1, CXCL8, and CCL20 secretion in response to IL-1β. In the presence of ATRA the supernatants of these cells induced CD103 expression on monocyte-derived dendritic cells and when conditioned by ATRA and cocultured with CD4(+) T-lymphocytes they reduced the proportion of Th17 T-cells. However, in the macrophage-T-cell cocultures the number of these effector T-cells was increased. Thus cytokine-activated colonic epithelial cells trigger the secretion of distinct combinations of chemokines depending on the proinflammatory stimulus and are controlled by retinoic acid, which also governs dendritic cell and macrophage responses.
维生素A在维持肠道内环境稳定中起着至关重要的作用，但迄今为止，其与趋化因子的相互作用尚未得到研究。我们使用体外模型系统，研究了人结肠上皮细胞（Caco2、HT - 29和HCT116）衍生的炎症刺激对单核细胞来源的树突状细胞和巨噬细胞的影响。未受刺激的Caco2和HT - 29细胞分泌CCL19、CCL21和CCL22趋化因子，这些趋化因子可以吸引树突状细胞和巨噬细胞，并通过视黄酸诱导CCR7受体上调，从而导致树突状细胞迁移。趋化因子Mk、CXCL16和CXCL7由所有测试的3种细胞系分泌，并且在IL - 1β或TNF - α刺激下，这种作用被全反式维甲酸（ATRA）抑制，但对IL - 1β刺激下CXCL1、CXCL8和CCL20的分泌没有影响。在存在ATRA的情况下，这些细胞的上清液诱导单核细胞来源的树突状细胞上CD103表达，并且当用ATRA处理并与CD4(+) T淋巴细胞共培养时，它们降低了Th17 T细胞的比例。然而，在巨噬细胞 - T细胞共培养中，这些效应T细胞的数量增加。因此，细胞因子激活的结肠上皮细胞根据促炎刺激触发不同趋化因子组合的分泌，并受视黄酸控制，视黄酸也调节树突状细胞和巨噬细胞的反应。
