英国纽卡斯尔大学Venetia Bigley团队在研究中取得进展。他们发现人树突状细胞（DCs）的两种发育途径需要不同浓度的IRF8转录因子。 这一研究成果在线发表在2020年7月30日出版的国际学术期刊《免疫》上。

使用高维分析、体外分化和人IRF8等位基因缺失谱系，研究人员证明了cDC2（CD1c + DC）异质性源于两种不同的发育途径。表达CD123和BTLA的接触淋巴IRF8^hi途径带有浆细胞样DC（pDC）、cDC1和DC2印记，而表达SIRPA的常见髓样IRF8^lo途径形成DC3和单核细胞。研究人员通过粒细胞-巨噬细胞祖细胞（GMP）区室追踪到不同的发育轨迹，表明AXL⁺ SIGLEC6⁺ pre-DC仅映射到DC2途径。为了满足对IRF8较低的需求，人DC3发育为替代部分IRF8缺乏症中的DC2。

据悉，哺乳动物DCs的形成受多种造血转录因子（包括IRF8）的调控。IRF8缺失对DC亚群（包括pDC和常规DC谱系cDC1和cDC2）产生不同的影响。在人体中已经发现了与cDC2相关的亚型，包括AXL⁺ SIGLEC6⁺ pre-DC、DC2和DC3。但这种异质性的起源是未知的。

附：英文原文

Title: Differential IRF8 Transcription Factor Requirement Defines Two Pathways of Dendritic Cell Development in Humans

Author: Urszula Cytlak, Anastasia Resteu, Sarah Pagan, Kile Green, Paul Milne, Sheetal Maisuria, David McDonald, Gillian Hulme, Andrew Filby, Benjamin Carpenter, Rachel Queen, Sophie Hambleton, Rosie Hague, Hana Lango Allen, James E.D. Thaventhiran, Gina Doody, Matthew Collin, Venetia Bigley

Issue&Volume: 2020-07-30

Abstract: The formation of mammalian dendritic cells (DCs) is controlled by multiple hematopoietic transcription factors, including IRF8. Loss of IRF8 exerts a differential effect on DC subsets, including plasmacytoid DCs (pDCs) and the classical DC lineages cDC1 and cDC2. In humans, cDC2-related subsets have been described including AXL+SIGLEC6+ pre-DC, DC2 and DC3. The origin of this heterogeneity is unknown. Using high-dimensional analysis, in vitro differentiation, and an allelic series of human IRF8 deficiency, we demonstrated that cDC2 (CD1c+DC) heterogeneity originates from two distinct pathways of development. The lymphoid-primed IRF8hi pathway, marked by CD123 and BTLA, carried pDC, cDC1, and DC2 trajectories, while the common myeloid IRF8lo pathway, expressing SIRPA, formed DC3s and monocytes. We traced distinct trajectories through the granulocyte-macrophage progenitor (GMP) compartment showing that AXL+SIGLEC6+ pre-DCs mapped exclusively to the DC2 pathway. In keeping with their lower requirement for IRF8, DC3s expand to replace DC2s in human partial IRF8 deficiency.

DOI: 10.1016/j.immuni.2020.07.003

Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30283-1