中文摘要：

我們通過定位克隆技術(shù)確定了Ym1基因（存在一個重復(fù)序列和一個啟動子多態(tài)性）是炎癥的一個主要調(diào)控因子。具有RIIIS/J單倍型（該單倍型不表達(dá)Ym1）的小鼠，對甘露聚糖增強(qiáng)的膠原抗體誘導(dǎo)性關(guān)節(jié)炎，以及由鼻內(nèi)暴露于甘露聚糖誘導(dǎo)的慢性關(guān)節(jié)炎，均表現(xiàn)出較低的易感性。 荷蘭Liposoma清除劑清除肺部巨噬細(xì)胞可緩解關(guān)節(jié)炎，而向Ym1缺陷小鼠鼻內(nèi)補(bǔ)充Ym1蛋白則逆轉(zhuǎn)了疾病進(jìn)程，這表明肺部巨噬細(xì)胞的Ym1在炎癥活性中起關(guān)鍵作用。

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.

論文信息：

論文題目：Natural polymorphism of Ym1 regulates pneumonitis through alternative activation of macrophages

期刊名稱：Science Advances

時間期卷：Vol 6, Issue43(2020)

在線時間：2020年10月21日

DOI: 10.1126/sciadv.aba9337

產(chǎn)品信息：

貨號：CP-005-005

規(guī)格：5ml+5ml

品牌：Liposoma

產(chǎn)地：荷蘭

名稱：Clodronate Liposomes&Control Liposomes

辦事處：靶點科技

Clodronate Liposomes氯膦酸鹽脂質(zhì)體清除肺炎模型小鼠體內(nèi)肺泡巨噬細(xì)胞。荷蘭Liposoma巨噬細(xì)胞清除劑ClodronateLiposomes見刊于Science Advances：Ym1的自然多態(tài)性通過巨噬細(xì)胞的替代性激活來調(diào)節(jié)肺炎。

Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes氯膦酸二鈉脂質(zhì)體清除巨噬細(xì)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.

巨噬細(xì)胞清除材料和方法文獻(xiàn)截圖：Ym1的自然多態(tài)性通過巨噬細(xì)胞的替代性激活來調(diào)節(jié)肺炎