美国马萨诸塞大学医学院Kenneth L. Rock研究组发现细胞死亡的免疫感知通过c型凝集素受体2d（Clec2d）识别组蛋白序列，从而引起炎症和组织损伤。相关论文于2019年12月16日在线发表于国际学术期刊《免疫》。

研究人员表示，免疫系统监视细胞的健康，并受到坏死的影响。

研究人员检查了驱动该反应的受体和配体。在C型凝集素受体的靶向筛选中，Clec2d报告分子对坏死细胞的裂解液产生了反应。生化纯化将组蛋白（包括游离的、结合至核小体的或者嗜中性粒细胞胞外陷阱的）鉴定为Clec2d配体。Clec2d识别组蛋白尾巴中的多碱基序列，这种识别对这些序列的翻译后修饰敏感。与WT小鼠相比，Clec2d^-/-小鼠在肝毒性损伤模型中对注射的组蛋白的促炎反应降低，组织损伤更少，存活率更高。在巨噬细胞中，Clec2d定位于质膜和内吞体。组蛋白与Clec2d的结合不会引起激酶激活或细胞因子的产生。而是，组蛋白结合的DNA以Clec2d依赖的方式刺激了内吞体Tlr9依赖的反应。因此，Clec2d结合坏死细胞死亡时释放的组蛋白，对炎症和组织损伤具有功能性后果。

附：英文原文

Title: Immune Sensing of Cell Death through Recognition of Histone Sequences by C-Type Lectin-Receptor-2d Causes Inflammation and Tissue Injury

Author: Jiann-Jyh Lai, Freidrich M. Cruz, Kenneth L. Rock

Issue&Volume: December 16, 2019

Abstract: The immune system monitors the health of cells and is stimulated by necrosis. Herewe examined the receptors and ligands driving this response. In a targeted screenof C-type lectin receptors, a Clec2d reporter responded to lysates from necrotic cells.Biochemical purification identified histones, both free and bound to nucleosomes orneutrophil extracellular traps, as Clec2d ligands. Clec2d recognized poly-basic sequencesin histone tails and this recognition was sensitive to post-translational modificationsof these sequences. As compared with WT mice, Clec2d/ mice exhibited reduced proinflammatory responses to injected histones, and less tissuedamage and improved survival in a hepatotoxic injury model. In macrophages, Clec2dlocalized to the plasma membrane and endosomes. Histone binding to Clec2d did notstimulate kinase activation or cytokine production. Rather, histone-bound DNA stimulatedendosomal Tlr9-dependent responses in a Clec2d-dependent manner. Thus, Clec2d bindsto histones released upon necrotic cell death, with functional consequences to inflammationand tissue damage.

DOI: 10.1016/j.immuni.2019.11.013

Source: https://www.cell.com/immunity/fulltext/S1074-7613(19)30494-7