中文摘要：
我们通过定位克隆技术确定了Ym1基因（存在一个重复序列和一个启动子多态性）是炎症的一个主要调控因子。具有RIIIS/J单倍型（该单倍型不表达Ym1）的小鼠，对甘露聚糖增强的胶原抗体诱导性关节炎，以及由鼻内暴露于甘露聚糖诱导的慢性关节炎，均表现出较低的易感性。 荷兰Liposoma清除剂清除肺部巨噬细胞可缓解关节炎，而向Ym1缺陷小鼠鼻内补充Ym1蛋白则逆转了疾病进程，这表明肺部巨噬细胞的Ym1在炎症活性中起关键作用。
Ym1缺陷小鼠在患上肺炎后，表现为嗜酸性粒细胞浸润减少，II型细胞因子和IgG1产生降低，并且由于STAT6激活增强，巨噬细胞向替代性激活方向偏移。蛋白质组学分析将Ym1多态性与脂质代谢的改变联系起来。Ym1缺陷巨噬细胞中被诱导的PPAR-γ和脂质代谢变化促进了细胞的极化。
总之，Ym1的自然多态性通过调控与肺部炎症相关的巨噬细胞替代性激活来发挥作用。
英文摘要：
We have positionally cloned the Ym1 gene, with a duplication and a promoter polymorphism, as a major regulator of inflammation. Mice with the RIIIS/J haplotype, with the absence of Ym1 expression, showed reduced susceptibility to mannan-enhanced collagen antibody–induced arthritis and to chronic arthritis induced by intranasal exposure of mannan. Depletion of lung macrophages alleviated arthritis, whereas intranasal supplement of Ym1 protein to Ym1-deficient mice reversed the disease, suggesting a key role of Ym1 for inflammatory activity by lung macrophages. Ym1-deficient mice with pneumonitis had less eosinophil infiltration, reduced production of type II cytokines and IgG1, and skewing of macrophages toward alternative activation due to enhanced STAT6 activation. Proteomics analysis connected Ym1 polymorphism with changed lipid metabolism. Induced PPAR-γ and lipid metabolism in Ym1-deficient macrophages contributed to cellular polarization. In conclusion, the natural polymorphism of Ym1 regulates alternative activation of macrophages associated with pulmonary inflammation.
论文信息：
论文题目：Natural polymorphism of Ym1 regulates pneumonitis through alternative activation of macrophages
期刊名称：Science Advances
时间期卷：Vol 6, Issue43(2020)
在线时间：2020年10月21日
DOI: 10.1126/sciadv.aba9337
产品信息：
货号：CP-005-005
规格：5ml+5ml
品牌：Liposoma
产地：荷兰
名称：Clodronate Liposomes&Control Liposomes
办事处：靶点科技
Clodronate Liposomes氯膦酸盐脂质体清除肺炎模型小鼠体内肺泡巨噬细胞。荷兰Liposoma巨噬细胞清除剂ClodronateLiposomes见刊于Science Advances：Ym1的自然多态性通过巨噬细胞的替代性激活来调节肺炎。
Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体清除巨噬细胞的材料和方法：
In vivo macrophage depletion
Mice with Ncf1 mutation were administrated intranasally with 20 mg of mannan to induce psoriasis and PsA (24) and were scored daily for arthritis severity using the same scoring system as mentioned above. The severity of the psoriasis-like skin manifestations was monitored on a 15-score system, in which ears or each paw was evaluated by a scale ranging from 1 to 3 (1, weak skin peeling; 2, moderate skin peeling; and 3, heavy skin peeling with some hair loss) (24). For the in vivo macrophage depletion experiment, 50 μl of clodronate-liposome or control PBS-liposome (Liposoma BV, The Netherlands) was administrated intranasally to mice 2 days before arthritis induction. The depletion efficiency was assessed by flow cytometry analysis. For the in vivo Ym1 protein supplement experiment, mice were intranasally administrated with mannan to induce arthritis at day 0, and recombinant Ym1 protein (1 μg per mouse; Sino Biological Inc.) was treated intranasally at days 0, 2, and 4 after arthritis induction.
巨噬细胞清除材料和方法文献截图：Ym1的自然多态性通过巨噬细胞的替代性激活来调节肺炎
