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不同祖系细胞为浆细胞样树突状细胞的异质性做出贡献。

Distinct progenitor lineages contribute to the heterogeneity of plasmacytoid dendritic cells.

机构信息

Department of Biomedicine, University of Basel, Basel, Switzerland.

Department of Human Genetics and VIB Center for the Biology of Disease, Leuven, Belgium.

出版信息

Nat Immunol. 2018 Jul;19(7):711-722. doi: 10.1038/s41590-018-0136-9. Epub 2018 Jun 20.

Abstract

Plasmacytoid dendritic cells (pDCs) are an immune subset devoted to the production of high amounts of type 1 interferons in response to viral infections. Whereas conventional dendritic cells (cDCs) originate mostly from a common dendritic cell progenitor (CDP), pDCs have been shown to develop from both CDPs and common lymphoid progenitors. Here, we found that pDCs developed predominantly from IL-7R lymphoid progenitor cells. Expression of SiglecH and Ly6D defined pDC lineage commitment along the lymphoid branch. Transcriptional characterization of SiglecHLy6D precursors indicated that pDC development requires high expression of the transcription factor IRF8, whereas pDC identity relies on TCF4. RNA sequencing of IL-7R lymphoid and CDP-derived pDCs mirrored the heterogeneity of mature pDCs observed in single-cell analysis. Both mature pDC subsets are able to secrete type 1 interferons, but only myeloid-derived pDCs share with cDCs their ability to process and present antigen.

摘要

浆细胞样树突状细胞(pDCs)是一种免疫亚群,能够在病毒感染时产生大量 I 型干扰素。虽然传统树突状细胞(cDCs)主要来源于共同的树突状细胞前体(CDP),但已证明 pDCs 可以由 CDP 和共同淋巴样前体发育而来。在这里,我们发现 pDCs 主要由 IL-7R 淋巴样前体细胞发育而来。SiglecH 和 Ly6D 的表达沿淋巴样分支定义了 pDC 谱系的承诺。SiglecH Ly6D 前体的转录特征表明,pDC 发育需要转录因子 IRF8 的高表达,而 pDC 特性依赖于 TCF4。IL-7R 淋巴样和 CDP 衍生的 pDC 的 RNA 测序反映了单细胞分析中观察到的成熟 pDC 异质性。这两个成熟的 pDC 亚群都能够分泌 I 型干扰素,但只有髓系来源的 pDCs 与 cDCs 一样具有加工和呈递抗原的能力。

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