Department of Immunology-Oncology, Maisonneuve-Rosemont Hospital, Montreal, Quebec H1T 2M4, Canada; and Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, Quebec H3C 3J7, Canada.
Department of Immunology-Oncology, Maisonneuve-Rosemont Hospital, Montreal, Quebec H1T 2M4, Canada; and Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, Quebec H3C 3J7, Canada
J Immunol. 2020 Oct 15;205(8):2117-2127. doi: 10.4049/jimmunol.2000742. Epub 2020 Sep 4.
Conventional dendritic cells (cDCs) are comprised of two major subsets, type 1 cDC (cDC1) and type 2 cDC (cDC2). As each cDC subset differentially influences the nature of immune responses, we sought factors that would allow the manipulation of their relative abundance. Notably, cDC1 are less abundant than cDC2 in both lymphoid and nonlymphoid organs. We demonstrate that this bias is already apparent in bone marrow precommitted precursors. However, comparison of five common inbred strains revealed a disparity in precursor-product relationship, in which mice with fewer precursors to cDC1 had more cDC1. This disparity associated with contrasting variations in CD135 (FLT3) expression on cDC subsets. Hence, we characterized the response to FLT3 ligand during cDC1 and cDC2 lineage differentiation and find that although FLT3 ligand is required throughout cDC2 differentiation, it is surprisingly dispensable during late-stage cDC1 differentiation. Overall, we find that tight regulation of FLT3 ligand levels throughout cDC differentiation dictates the cDC1 to cDC2 ratio in lymphoid organs.
常规树突状细胞 (cDC) 分为两个主要亚群，即 1 型 cDC (cDC1) 和 2 型 cDC (cDC2)。由于每个 cDC 亚群对免疫反应的性质有不同的影响，我们寻求能够操纵它们相对丰度的因素。值得注意的是，cDC1 在淋巴器官和非淋巴器官中的丰度均低于 cDC2。我们证明这种偏向性在骨髓前体细胞中已经很明显。然而，对五种常见近交系的比较显示，前体细胞-产物关系存在差异，其中 cDC1 前体细胞较少的小鼠具有更多的 cDC1。这种差异与 cDC 亚群上 CD135 (FLT3) 表达的明显变化相关。因此，我们描述了在 cDC1 和 cDC2 谱系分化过程中对 FLT3 配体的反应，发现虽然 FLT3 配体在整个 cDC2 分化过程中是必需的，但在晚期 cDC1 分化过程中却出乎意料地不需要。总的来说，我们发现 FLT3 配体在整个 cDC 分化过程中的严格调节决定了淋巴器官中 cDC1 与 cDC2 的比例。
