近日，华盛顿大学医学院Marco Colonna及其研究小组的研究认为，不同谱系的祖细胞形成成熟的2型常规树突状细胞的多样性。相关论文于2024年5月30日发表于国际顶尖学术期刊《免疫》杂志上。

通过生成Cd300c^iCre-hCD2R26^tdTomato报告小鼠，该团队在体外和体内鉴定出了一种骨髓前cDC2祖细胞，该祖细胞只能生成cDC2。单细胞分析和多参数流式细胞术显示，前cDC2包括髓源性前cDC2和淋巴源性浆细胞样DC (pDC)样前体，分化为转录趋同的cDC2表型。

与Ms4a3^Cre R26^tdTomato谱系追踪的DC3(一种绕过CDP的单核细胞DC祖细胞(MDP)衍生亚群)相比，Cd300c追踪的cDC2具有不同的转录组学特征、表型和组织分布。Cd300c追踪的cDC2减少的小鼠对T细胞依赖性抗原的体液反应受损。该研究组得出结论，不同谱系的祖细胞塑造了成熟cDC2跨组织的多样性。因此，个体发生可能影响组织免疫反应。

据了解，经典树突状细胞(cDC)是由cDC1和cDC2组成的抗原呈递细胞，分别负责启动初始CD8⁺和CD4⁺ T细胞。最近的研究揭示了cDC2的异质性，并发现了除常见DC祖细胞(CDP)外的多种cDC2祖细胞，暗示了不同的cDC2谱系。

附：英文原文

Title: Progenitors of distinct lineages shape the diversity of mature type 2 conventional dendritic cells

Author: Patrick Fernandes Rodrigues, Tihana Trsan, Grozdan Cvijetic, Darya Khantakova, Santosh K. Panda, Zhaoyuan Liu, Florent Ginhoux, Marina Cella, Marco Colonna

Issue&Volume: 2024-05-30

Abstract: Conventional dendritic cells (cDC) are antigen-presenting cells comprising cDC1 and cDC2, responsible for priming naive CD8+ and CD4+ T cells, respectively. Recent studies have unveiled cDC2 heterogeneity and identified various cDC2 progenitors beyond the common DC progenitor (CDP), hinting at distinct cDC2 lineages. By generating Cd300ciCre-hCD2R26tdTomato reporter mice, we identified a bone marrow pro-cDC2 progenitor exclusively generating cDC2 in vitro and in vivo. Single-cell analyses and multiparametric flow cytometry demonstrated that pro-cDC2 encompasses myeloid-derived pre-cDC2 and lymphoid-derived plasmacytoid DC (pDC)-like precursors differentiating into a transcriptionally convergent cDC2 phenotype. Cd300c-traced cDC2 had distinct transcriptomic profiles, phenotypes, and tissue distributions compared with Ms4a3CreR26tdTomato lineage-traced DC3, a monocyte-DC progenitor (MDP)-derived subset that bypasses CDP. Mice with reduced Cd300c-traced cDC2 showed impaired humoral responses to T cell-dependent antigens. We conclude that progenitors of distinct lineages shape the diversity of mature cDC2 across tissues. Thus, ontogenesis may impact tissue immune responses.

DOI: 10.1016/j.immuni.2024.05.007

Source: https://www.cell.com/immunity/fulltext/S1074-7613(24)00260-7