亚洲国产成人无码AV在线播放,亚洲色偷拍另类无码专区,亚洲AV日韩AV永久无码久久,国产手机在线精品

技術(shù)文章您現(xiàn)在的位置:首頁 > 技術(shù)文章 > JEM期刊氯膦酸鹽脂質(zhì)體清除肺泡巨噬細(xì)胞專業(yè)論文

JEM期刊氯膦酸鹽脂質(zhì)體清除肺泡巨噬細(xì)胞專業(yè)論文

更新時間:2024-11-20   點(diǎn)擊次數(shù):413次

中文摘要:

肺泡巨噬細(xì)胞 (AM) 是專門的組織駐留巨噬細(xì)胞,可在過敏性炎癥和哮喘中協(xié)調(diào)免疫反應(yīng)。然而,是什么信號指示 AM 與其他免疫細(xì)胞進(jìn)行串?dāng)_仍不清楚。在這里,我們報道了自分泌運(yùn)動因子受體 (AMFR),一種內(nèi)質(zhì)網(wǎng)駐留的 E3 泛素連接酶,在哮喘的 AM 中上調(diào),對這種情況至關(guān)重要。AMFR 缺乏顯著降低過敏誘導(dǎo)的輔助性 T 細(xì)胞 2 (Th2) 和嗜酸性粒細(xì)胞炎癥,AM 中粒細(xì)胞-巨噬細(xì)胞集落刺激因子 (GM-CSF) 的產(chǎn)生較少。從機(jī)制上講,在胸腺基質(zhì)淋巴細(xì)胞生成素 (TSLP) 刺激后,AMFR 與細(xì)胞因子誘導(dǎo)的含 SH2 的蛋白 (CIS) 直接相關(guān),誘導(dǎo) CIS 的 Lys48 連接的多泛素化的泛素化,從而阻斷了 CIS 對信號轉(zhuǎn)導(dǎo)和轉(zhuǎn)錄激活因子 5 (STAT5) 磷酸化和 AM 下游途徑激活的抑制作用??傊覀兊慕Y(jié)果表明,AMFR 通過調(diào)節(jié) AM 功能在促進(jìn)哮喘炎癥中起關(guān)鍵作用,并可能成為哮喘治療的新潛在藥物靶點(diǎn)。

英文摘要:

Alveolar macrophages (AMs) are specialized tissue-resident macrophages that orchestrate the immune response in allergic inflammation and asthma. However, what signals direct AMs to cross talk with other immune cells remains unclear. Here, we report that autocrine motility factor receptor (AMFR), an endoplasmic reticulum–resident E3 ubiquitin ligase, is upregulated in AMs of asthma and is critical for this condition. AMFR deficiency significantly decreased allergy-induced T helper 2 (Th2) and eosinophilic inflammation, with less granulocyte-macrophage colony-stimulating factor (GM-CSF) production in AMs. Mechanistically, following thymic stromal lymphopoietin (TSLP) stimulation, AMFR associated directly with cytokine-inducible SH2-containing protein (CIS), induced the ubiquitination of Lys48-linked polyubiquitination of CIS, and consequently blocked the inhibitory effect of CIS on signal transducer and activator of transcription 5 (STAT5) phosphorylation and the downstream pathway activation in AMs. In conclusion, our results demonstrate that AMFR serves a crucial role in promoting inflammation in asthma through regulating AM function, and may emerge as a new potential drug target for asthma therapy.



論文信息:

論文題目: AMFR drives allergic asthma development by promoting alveolar macrophage–derived GM-CSF production

期刊名稱:JEM- J Exp Med

時間期卷: (2022) 219 (5): e20211828

在線時間:2022年3月25日

DOI: doi.org/10.1084/jem.20211828


Liposoma巨噬細(xì)胞清除劑氯膦酸鹽脂質(zhì)體Clodronate Liposomes見刊于JEM:

JEM期刊氯膦酸鹽脂質(zhì)體清除肺泡巨噬細(xì)胞專業(yè)論文


Liposoma巨噬細(xì)胞清除劑氯膦酸鹽脂質(zhì)體Clodronate Liposomes的材料和方法

JEM期刊氯膦酸鹽脂質(zhì)體清除肺泡巨噬細(xì)胞專業(yè)論文

JEM期刊率膦酸鹽脂質(zhì)體清除肺泡巨噬細(xì)胞專業(yè)論文:肺泡巨噬細(xì)胞清除解決方案

Reagents

OVA (A5503), papain (76216), chitin (C9752), collagenase D (11088866001), and DNase I (10104159001) were obtained from Sigma-Aldrich. The Imject Alum adjuvant (77161) and ER-TrackerTM Blue-White DPX (E12353) were purchased from Thermo Fisher Scientific. Clodronate liposomes (CP-005-005) were purchased from Liposoma. The recombinant murine (555-TS) and human (1398-TS) TSLP cytokines were purchased from R&D. Recombinant murine GM-CSF (315-03) and M-CSF (315-02) were from PeproTech. The anti-AMFR (ab76841) antibody was obtained from Abcam. The anti-CIS antibody (sc-166326) was obtained from Santa Cruz Biotechnology. The anti-CD68 antibody (14-0681-80) was purchased from Invitrogen Thermo Fisher Scientific. Antibodies for Myc-Tag (2272S and 2276S), Flag-Tag (14793S), HA-Tag (3724S), β-actin (8457S), Ub (3936S), STAT5 (94205S), phospho-STAT5 (9351L), phospho-JAK1 (74129T), JAK1 (3344T), phospho-JAK2 (8082T), JAK2, (3230T), SOCS1 (3950T), SOCS2 (2779P), SOCS3 (2932P), Alexa Fluor 594 anti-mouse IgG (8890S), and Alexa Fluor 488 anti-rabbit IgG (4412S) were obtained from Cell Signaling Technology. The secondary antibodies peroxidase-conjugated anti-rabbit (111-035-003) and anti-mouse (115-035-003) were purchased from Jackson ImmunoResearch Laboratories. The flow cytometry antibodies, including APC anti-mouse CD11c (117310), FITC anti-mouse Siglec-F (155504), PE anti-mouse Siglec-F (155506), APC anti-mouse/human CD11b (101212), PE/Cyanine7 anti-mouse CD45 (103114), PerCP/Cyanine5.5 anti-mouse CD64 (139307), APC/Fire 750 anti-mouse Ly-6G (127652), Brilliant Violet 650 anti-mouse F4/80 (123149), Brilliant Violet 421 anti-mouse/human CD11b (101235), FITC anti-mouse I-A/I-E (MHC class II; 107605), PE anti-human GM-CSF (502305), and PE/Cyanine7 anti-mouse GM-CSF (505411), were from BioLegend. The BCA protein assay kit (P0012S) and DAPI (C1002) were obtained from Beyotime.

AM adoptive transfer

Adoptive transfer of AMs was performed as previously reported (Miki et al., 2021; Qian et al., 2015). For in vivo deletion of macrophages in lung tissues, mice were sensitized with OVA as described above and treated with 40 μl of clodronate liposome i.t. for two successive days (days 18 and 19). For the AM adoptive transfer study, AMs derived from WT or AMFR knockout mice were then transferred by i.t. injection into the lungs of clodronate liposome-treated and OVA-sensitized WT mice at a density of 5 × 105 cells/mouse (40 μl) on day 20. 24 h after AM delivery, the mice were i.t. challenged with OVA for three days (days 21, 22, and 23). On day 25, the mice were sacrificed to analyze allergic asthmatic inflammation (Fig. 3 A).



靶點(diǎn)科技(北京)有限公司

靶點(diǎn)科技(北京)有限公司

地址:中關(guān)村生命科學(xué)園北清創(chuàng)意園2-4樓2層

© 2025 版權(quán)所有:靶點(diǎn)科技(北京)有限公司  備案號:京ICP備18027329號-2  總訪問量:293724  站點(diǎn)地圖  技術(shù)支持:化工儀器網(wǎng)  管理登陸

大胆人体艺术| 蜜臀av人妻国产精品李丽| 父辈的荣耀高清完整免费观看| 与上司出轨的人妻| 十大禁用软件app黄台大全下载| 成人视频在线观看| 暴露放荡的娇妻| 性色av浪潮av蜜桃av| s货c货大声点叫| 羞羞答答麻豆国产免费观看| 欧美国产高清欧美内衣办| japanese55丰满成熟| 麻豆国产av国片精品有毛| 日韩大片高清播放器| 金梅瓶在线观看| 三级片在线| 再深点灬舒服灬太大了添gif| 一色一伦一区二区三区| 熟睡人妻被讨厌的公侵犯深田咏美| 日日狠狠久久偷偷色综合96蜜桃 | 国产精品黄黄久久久免费看| 后入式动态图| 亚洲麻豆AV无码成人片在线观看 | 大炕上和亲亲公个取所需| 精品久久久久久无码专区不卡| 狠狠色噜噜狠狠狠狠av| 少妇无码av无码专区线| 无码任你躁久久久久久老妇| AV无码久久久久不卡蜜桃 | 国产激情无码一区二区APP| 国内精品久久久人妻中文字幕| 久久精品国产亚洲7777| 性vodafonewifi| 国产精品久久久亚洲偷窥女厕| 啦啦啦资源视频在线观看8| 后入内射无码人妻一区| 51精品国产人成在线观看| 国产成人A亚洲精V品无码| 13小男生gay自慰脱裤子| 精品人妻无码一区二区色欲产成人| 免费观看黄网站|