Abstract NKp44 is a human receptor originally found on activated NK cells, group 1 and group 3 innate lymphoid cells that binds dimers of platelet-derived growth factor D (PDGF-DD). NKp44 is also expressed on tissue plasmacytoid dendritic cells (PDCs), but NKp44-PDGF-DD interaction on PDCs remains unstudied. Engagement of NKp44 with PDGF-DD in vitro enhanced PDC secretion of IFN-α, TNF, and IL-6 in response to the TLR9 ligand CpG-ODN, but not TLR7/8 ligands. In tissues, PDCs were found in close contact with PDGF-DD–expressing cells in the high endothelial venules and epithelium of tonsils, melanomas, and skin lesions infected with Molluscum contagiosum. Recombinant PDGF-DD enhanced the serum IFN-α response to systemic HSV-1 infection in a humanized mouse model. We conclude that NKp44 integrates with TLR9 signaling to enhance PDC cytokine production. These findings may have bearings for immune responses to TLR9-based adjuvants, therapy for tumors expressing PDGF-DD, and infections with DNA viruses that induce PDGF-DD expression to enhance viral spread.

中文翻译：

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最前沿：PDGF-DD 与 NKp44 结合共同刺激人浆细胞样树突状细胞中的 TLR9 信号传导和促炎细胞因子分泌

摘要NKp44 是一种人类受体，最初发现于活化的 NK 细胞、第 1 组和第 3 组先天淋巴细胞上，可结合血小板衍生生长因子 D (PDGF-DD) 二聚体。NKp44 也在组织浆细胞样树突状细胞 (PDC) 上表达，但 NKp44-PDGF-DD 在 PDC 上的相互作用尚未研究。NKp44 与 PDGF-DD 的体外结合增强了 PDC 对 TLR9 配体 CpG-ODN 的 IFN-α、TNF 和 IL-6 分泌，但对 TLR7/8 配体没有反应。在组织中，PDC 被发现与扁桃体、黑色素瘤和传染性软疣感染的皮肤病变的高内皮微静脉和上皮中表达 PDGF-DD 的细胞密切接触。在人源化小鼠模型中，重组 PDGF-DD 增强了血清 IFN-α 对全身 HSV-1 感染的反应。我们得出的结论是 NKp44 与 TLR9 信号传导整合以增强 PDC 细胞因子的产生。这些发现可能与基于 TLR9 的佐剂的免疫反应、表达 PDGF-DD 的肿瘤的治疗以及诱导 PDGF-DD 表达以增强病毒传播的 DNA 病毒感染有关。