Anhui Provincial Key Laboratory for Conservation and Exploitation of Biological Resources, School of Life Science, Anhui Normal University, Wuhu 241000, China.
Anhui Provincial Key Laboratory for Conservation and Exploitation of Biological Resources, School of Life Science, Anhui Normal University, Wuhu 241000, China.
Cell Immunol. 2018 Sep;331:100-109. doi: 10.1016/j.cellimm.2018.06.001. Epub 2018 Jun 7.
Dendritic cells (DCs) contain heterogeneous populations, with classical DCs developed at steady state and monocyte-derived DCs mobilized under inflammatory conditions, although their total numbers in vivo are scares. To obtain enough quantity for immunological study or clinical application, we have previously established that bone marrow-derived DCs in the presence of Flt-3L (FL-DCs) or GM-CSF (GM-DCs) in vitro are equivalent to the steady state DCs and inflammatory DCs in vivo respectively. What difference, however, exists between these two most commonly used culture systems in DC functions and survival, and how does it correlate to the division of works by their corresponding counterparts in vivo remain ill-defined. In this study, we found that GM-DCs of inflammatory nature were more phagocytic, potent at inducing Th2 and Th17 differentiation, and had longer survival rate, whereas FL-DCs of steady state characters were stronger T cell activator and better at directing Th1 differentiation. Mechanistically, NO production induced by the LPS-activated GM-DCs could partly explain for their failure to improve T cell proliferation, and the distinct T cell differentiation profiles and viability demonstrated by the two types of DCs were underpinned by their preferential secretion of T cell polarizing cytokines and expression of anti-apoptotic genes. Such disparate functionalities and survival potentials of steady state and inflammatory DCs in vitro fit in well with their respective roles in vivo in particular immunological settings and have serious implications in translational applications.
树突状细胞 (DCs) 包含异质性群体，其中经典的 DCs 在稳态下发育，单核细胞衍生的 DCs 在炎症条件下动员，尽管它们在体内的总数很少。为了获得足够数量用于免疫研究或临床应用，我们之前已经证明，在 Flt-3L（FL-DCs）或 GM-CSF（GM-DCs）存在下体外骨髓来源的 DC 分别等同于体内稳态 DC 和炎症 DC。然而，这两种最常用的培养系统在 DC 功能和存活方面存在哪些差异，以及它如何与体内对应物的分工相关，仍然不清楚。在这项研究中，我们发现具有炎症性质的 GM-DCs 具有更强的吞噬能力，能够更强地诱导 Th2 和 Th17 分化，并且具有更长的存活率，而具有稳态特征的 FL-DCs 则是更强的 T 细胞激活剂，更擅长指导 Th1 分化。从机制上讲，LPS 激活的 GM-DCs 产生的 NO 可部分解释其不能改善 T 细胞增殖的原因，两种类型的 DC 表现出不同的 T 细胞分化谱和存活率，这是由它们优先分泌 T 细胞极化细胞因子和表达抗凋亡基因所支撑的。体外稳态和炎症 DC 的这种不同功能和存活潜力与它们在特定免疫环境中的体内各自作用非常吻合，并对转化应用具有重要意义。
