The Walter & Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia.
Immunol Cell Biol. 2020 Mar;98(3):203-214. doi: 10.1111/imcb.12313. Epub 2020 Feb 5.
The NZB/W F1 (F1) mice develop severe disease that is similar to human systemic lupus erythematosus. By contrast, each parent strain, NZB or NZW, has limited autoimmunity, suggesting traits of both strains contribute to pathogenesis. Although many of the contributing genes have been identified, the contributing cellular abnormality associated with each parent strain remains unresolved. Given that plasmacytoid dendritic cells (pDCs) are key to the pathogenesis of lupus, we investigated the properties of pDCs from NZB and NZW mice. We found that NZB mouse had higher numbers of pDCs, with much of the increase being contributed by a more abundant CD8 pDC subset. This was associated with prolonged survival and stronger proliferation of CD4 T cells. By contrast, NZW pDCs had heightened capacity to produce interferon-α (IFNα) and IFNλ, and promoted stronger B-cell proliferation upon CpG stimulation. Thus, our data reveal the different functional and numerical characteristics of pDCs from NZW and NZB mouse.
NZB/W F1 (F1) 小鼠发生严重的疾病，类似于人类系统性红斑狼疮。相比之下，每个亲本品系，NZB 或 NZW，具有有限的自身免疫性，这表明两种品系的特征都有助于发病机制。尽管已经确定了许多相关基因，但与每个亲本品系相关的细胞异常仍未得到解决。鉴于浆细胞样树突状细胞 (pDC) 是狼疮发病机制的关键，我们研究了 NZB 和 NZW 小鼠的 pDC 特性。我们发现 NZB 小鼠的 pDC 数量较高，其中大部分增加归因于更丰富的 CD8 pDC 亚群。这与 CD4 T 细胞的存活时间延长和增殖能力增强有关。相比之下，NZW pDC 具有更高的产生干扰素-α (IFNα) 和 IFNλ 的能力，并且在 CpG 刺激下促进更强的 B 细胞增殖。因此，我们的数据揭示了来自 NZW 和 NZB 小鼠的 pDC 的不同功能和数量特征。
