Department of Hematology, Oncology and Stem Cell Transplantation, University Children's Hospital, University of Würzburg, Würzburg, Germany.
Front Immunol. 2019 Jun 28;10:1484. doi: 10.3389/fimmu.2019.01484. eCollection 2019.
Interleukin 10 is a central regulator of the antigen-presenting function of myeloid cells. It exerts immunomodulatory effects and induces a regulatory phenotype in monocyte-derived cells . We analyzed phenotype and function of monocytic cells in relation to the cytokine milieu and the timing of TLR-based activation. In GM-CSF/IL-4 cultured human monocytic cells, we identified two, mutually exclusive cell populations arising from undifferentiated cells: CD83 fully activated dendritic cells and CD14 macrophage like cells. Re-expression of CD14 occurs primarily after a sequential trigger with a TLR signal following IL-10 preincubation. This cell population with re-expressed CD14 greatly differs in phenotype and function from the CD83 cells. Detailed analysis of individual subpopulations reveals that exogenous IL-10 is critical for inducing the shift toward the CD14+ population, but does not affect individual changes in marker expression or cell function in most cases. Thus, plasticity of CD14 expression, defining a subset of immunoregulatory cells, is highly relevant for the composition of cellular products (such as DC vaccines) as it affects the function of the total product.
白细胞介素 10 是髓样细胞抗原呈递功能的核心调节因子。它发挥免疫调节作用，并在单核细胞来源的细胞中诱导调节表型。我们分析了与细胞因子环境和 TLR 激活时间相关的单核细胞的表型和功能。在 GM-CSF/IL-4 培养的人单核细胞中，我们从未分化细胞中鉴定出两种相互排斥的细胞群：完全激活的树突状细胞 CD83 和 CD14 巨噬样细胞。CD14 的重新表达主要发生在 TLR 信号继 IL-10 预孵育之后的顺序触发之后。具有重新表达的 CD14 的这种细胞群在表型和功能上与 CD83 细胞有很大的不同。对各个亚群的详细分析表明，外源性 IL-10 对于诱导向 CD14+ 群体的转变至关重要，但在大多数情况下不会影响标记表达或细胞功能的个体变化。因此，CD14 表达的可塑性，定义了一个免疫调节细胞亚群，对于细胞产物（如 DC 疫苗）的组成非常重要，因为它影响了总产物的功能。
