Sivakumaran Shivajanani, Henderson Stephen, Ward Sophie, Sousa Pedro Santos E, Manzo Teresa, Zhang Lei, Conlan Thomas, Means Terry K, D'Aveni Maud, Hermine Olivier, Rubio Marie-Thérèse, Chakraverty Ronjon, Bennett Clare L
Institute for Immunity and Transplantation, University College London, London, UK.
Cancer Institute, University College London, London, UK.
Eur J Immunol. 2016 Jan;46(1):192-203. doi: 10.1002/eji.201545789. Epub 2015 Nov 30.
Dendritic cells (DCs) play a vital role in innate and adaptive immunities. Inducible depletion of CD11c(+) DCs engineered to express a high-affinity diphtheria toxin receptor has been a powerful tool to dissect DC function in vivo. However, despite reports showing that loss of DCs induces transient monocytosis, the monocyte population that emerges and the potential impact of monocytes on studies of DC function have not been investigated. We found that depletion of CD11c(+) cells from CD11c.DTR mice induced the expansion of a variant CD64(+) Ly6C(+) monocyte population in the spleen and blood that was distinct from conventional monocytes. Expansion of CD64(+) Ly6C(+) monocytes was independent of mobilization from the BM via CCR2 but required the cytokine, G-CSF. Indeed, this population was also expanded upon exposure to exogenous G-CSF in the absence of DC depletion. CD64(+) Ly6C(+) monocytes were characterized by upregulation of innate signaling apparatus despite the absence of inflammation, and an increased capacity to produce TNF-α following LPS stimulation. Thus, depletion of CD11c(+) cells induces expansion of a unique CD64(+) Ly6C(+) monocyte population poised to synthesize TNF-α. This finding will require consideration in experiments using depletion strategies to test the role of CD11c(+) DCs in immunity.
树突状细胞（DCs）在先天性免疫和适应性免疫中发挥着至关重要的作用。通过基因工程改造使其表达高亲和力白喉毒素受体从而诱导性清除CD11c(+) DCs，已成为在体内剖析DC功能的有力工具。然而，尽管有报道显示DCs的缺失会诱导短暂的单核细胞增多，但出现的单核细胞群体以及单核细胞对DC功能研究的潜在影响尚未得到研究。我们发现，从CD11c.DTR小鼠中清除CD11c(+)细胞会诱导脾脏和血液中一种与传统单核细胞不同的变体CD64(+) Ly6C(+)单核细胞群体的扩增。CD64(+) Ly6C(+)单核细胞的扩增不依赖于通过CCR2从骨髓动员，但需要细胞因子G-CSF。事实上，在没有DC清除的情况下，暴露于外源性G-CSF时该群体也会扩增。CD64(+) Ly6C(+)单核细胞的特征是尽管没有炎症但先天性信号传导装置上调，并且在LPS刺激后产生TNF-α的能力增加。因此，CD11c(+)细胞的清除会诱导一个准备合成TNF-α的独特CD64(+) Ly6C(+)单核细胞群体的扩增。在使用清除策略来测试CD11c(+) DCs在免疫中的作用的实验中，这一发现需要加以考虑。
