Department of Microbiology & Immunology, Medical University of South Carolina, Charleston, SC, USA.
Department of Comparative Medicine, Medical University of South Carolina, Charleston, SC, USA.
Sci Rep. 2017 Nov 14;7(1):15552. doi: 10.1038/s41598-017-15791-x.
Sphingolipids regulate critical cellular processes including inflammation. Ceramide, which serves a central role in sphingolipid metabolism, is generated by six ceramide synthases (CerS) that differ in substrate specificity. CerS6 preferentially generates C-ceramide and its mRNA is highly expressed in immune tissues. In this study we analyzed how deficiency of CerS6 impacts on the development of colitis using an adoptive transfer model. Adoptive transfer of CerS6-deficient splenocytes, which have significantly decreased levels of C-ceramide, showed that CerS6-deficiency protected against the development of colitis. However, adoptively transferred cells isolated from the lamina propria of the large intestine from wild type or CerS6-deficient groups showed no differences in the percentages of immune-suppressive regulatory T cells, pro-inflammatory Th17 cells, or their ability to express IL-17. In vitro polarization of wild type or CerS6-deficient splenocytes also revealed no defects in the development of T cell subsets. Our data suggest that protection from colitis following adoptive transfer of CerS6-deficient splenocytes maybe related to their ability to migrate and proliferate in vivo rather than subset development or cytokine expression.
鞘脂类调节包括炎症在内的关键细胞过程。神经酰胺在鞘脂代谢中起着核心作用，它是由六种在底物特异性上有所不同的神经酰胺合酶（CerS）产生的。CerS6 优先生成 C 神经酰胺，其 mRNA 在免疫组织中高度表达。在这项研究中，我们使用过继转移模型分析了 CerS6 缺乏对结肠炎发展的影响。CerS6 缺陷的脾细胞过继转移显示，CerS6 缺乏可预防结肠炎的发生。然而，从野生型或 CerS6 缺陷型组的大肠固有层分离的过继转移细胞在免疫抑制性调节性 T 细胞、促炎性 Th17 细胞的百分比或其表达 IL-17 的能力方面没有差异。野生型或 CerS6 缺陷型脾细胞的体外极化也未显示 T 细胞亚群发育的缺陷。我们的数据表明，过继转移 CerS6 缺陷的脾细胞可预防结肠炎，这可能与它们在体内迁移和增殖的能力有关，而不是与细胞亚群发育或细胞因子表达有关。
