• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

白细胞介素-16 的中和作用通过 CCL4 依赖性机制保护非肥胖型糖尿病小鼠免于自身免疫性 1 型糖尿病。

Neutralization of interleukin-16 protects nonobese diabetic mice from autoimmune type 1 diabetes by a CCL4-dependent mechanism.

机构信息

Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada.

出版信息

Diabetes. 2010 Nov;59(11):2862-71. doi: 10.2337/db09-0131. Epub 2010 Aug 6.

DOI:10.2337/db09-0131
PMID:20693344
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2963545/
Abstract

OBJECTIVE

The progressive infiltration of pancreatic islets by lymphocytes is mandatory for development of autoimmune type 1 diabetes. This inflammatory process is mediated by several mediators that are potential therapeutic targets to arrest development of type 1 diabetes. In this study, we investigate the role of one of these mediators, interleukin-16 (IL-16), in the pathogenesis of type 1 diabetes in NOD mice.

RESEARCH DESIGN AND METHODS

At different stages of progression of type 1 diabetes, we characterized IL-16 in islets using GEArray technology and immunoblot analysis and also quantitated IL-16 activity in cell migration assays. IL-16 expression was localized in islets by immunofluorescence and confocal imaging. In vivo neutralization studies were performed to assess the role of IL-16 in the pathogenesis of type 1 diabetes.

RESULTS

The increased expression of IL-16 in islets correlated with the development of invasive insulitis. IL-16 immunoreactivity was found in islet infiltrating T-cells, B-cells, NK-cells, and dendritic cells, and within an insulitic lesion, IL-16 was derived from infiltrating cells. CD4(+) and CD8(+) T-cells as well as B220(+) B-cells were identified as sources of secreted IL-16. Blockade of IL-16 in vivo protected against type 1 diabetes by interfering with recruitment of CD4(+) T-cells to the pancreas, and this protection required the activity of the chemokine CCL4.

CONCLUSIONS

IL-16 production by leukocytes in islets augments the severity of insulitis during the onset of type 1 diabetes. IL-16 and CCL4 appear to function as counterregulatory proteins during disease development. Neutralization of IL-16 may represent a novel therapy for the prevention of type 1 diabetes.

摘要

目的

淋巴细胞渐进性浸润胰岛是自身免疫 1 型糖尿病发展的必要条件。这个炎症过程由几种介质介导，这些介质是阻止 1 型糖尿病发展的潜在治疗靶点。在这项研究中，我们研究了这些介质之一白细胞介素 16（IL-16）在 NOD 小鼠 1 型糖尿病发病机制中的作用。

研究设计和方法

在 1 型糖尿病进展的不同阶段，我们使用 GEArray 技术和免疫印迹分析对胰岛中的 IL-16 进行了特征分析，并用细胞迁移实验定量了 IL-16 活性。用免疫荧光和共聚焦成像对胰岛中的 IL-16 进行了定位。进行体内中和研究以评估 IL-16 在 1 型糖尿病发病机制中的作用。

结果

胰岛中 IL-16 的表达增加与侵袭性胰岛炎的发展相关。在胰岛浸润的 T 细胞、B 细胞、NK 细胞和树突状细胞以及胰岛炎病变中均发现 IL-16 免疫反应性，并且 IL-16 源自浸润细胞。CD4(+)和 CD8(+)T 细胞以及 B220(+)B 细胞被鉴定为分泌 IL-16 的来源。体内阻断 IL-16 通过干扰 CD4(+)T 细胞向胰腺的募集来预防 1 型糖尿病，这种保护作用需要趋化因子 CCL4 的活性。

结论

胰岛白细胞产生的 IL-16 增加了 1 型糖尿病发病期间胰岛炎的严重程度。IL-16 和 CCL4 在疾病发展过程中似乎作为拮抗蛋白发挥作用。IL-16 的中和可能代表预防 1 型糖尿病的一种新疗法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63c7/2963545/0ff5d06eec0c/zdb0111063250008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63c7/2963545/23665e76f27e/zdb0111063250001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63c7/2963545/78c02f21c7b0/zdb0111063250002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63c7/2963545/9e750fd8216a/zdb0111063250003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63c7/2963545/6bbb998dc6db/zdb0111063250004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63c7/2963545/a44f6a2966ad/zdb0111063250005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63c7/2963545/9e2862265703/zdb0111063250006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63c7/2963545/5dac9087f3e3/zdb0111063250007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63c7/2963545/0ff5d06eec0c/zdb0111063250008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63c7/2963545/23665e76f27e/zdb0111063250001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63c7/2963545/78c02f21c7b0/zdb0111063250002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63c7/2963545/9e750fd8216a/zdb0111063250003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63c7/2963545/6bbb998dc6db/zdb0111063250004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63c7/2963545/a44f6a2966ad/zdb0111063250005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63c7/2963545/9e2862265703/zdb0111063250006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63c7/2963545/5dac9087f3e3/zdb0111063250007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63c7/2963545/0ff5d06eec0c/zdb0111063250008.jpg

相似文献

1
Neutralization of interleukin-16 protects nonobese diabetic mice from autoimmune type 1 diabetes by a CCL4-dependent mechanism.白细胞介素-16 的中和作用通过 CCL4 依赖性机制保护非肥胖型糖尿病小鼠免于自身免疫性 1 型糖尿病。
Diabetes. 2010 Nov;59(11):2862-71. doi: 10.2337/db09-0131. Epub 2010 Aug 6.
2
Temporal relationship between immune cell influx and the expression of inducible nitric oxide synthase, interleukin-4 and interferon-gamma in pancreatic islets of NOD mice following adoptive transfer of diabetic spleen cells.糖尿病脾细胞过继转移后，NOD小鼠胰岛中免疫细胞浸润与诱导型一氧化氮合酶、白细胞介素-4和干扰素-γ表达之间的时间关系。
Histochem J. 2000 Apr;32(4):195-206. doi: 10.1023/a:1004084232446.
3
Local expression of transgene encoded TNF alpha in islets prevents autoimmune diabetes in nonobese diabetic (NOD) mice by preventing the development of auto-reactive islet-specific T cells.胰岛中转基因编码的肿瘤坏死因子α的局部表达通过阻止自身反应性胰岛特异性T细胞的发育，预防非肥胖糖尿病（NOD）小鼠发生自身免疫性糖尿病。
J Exp Med. 1996 Nov 1;184(5):1963-74. doi: 10.1084/jem.184.5.1963.
4
Pancreatic IL-4 expression results in islet-reactive Th2 cells that inhibit diabetogenic lymphocytes in the nonobese diabetic mouse.胰腺白细胞介素-4的表达会导致胰岛反应性Th2细胞的产生，这些细胞可抑制非肥胖糖尿病小鼠中的致糖尿病淋巴细胞。
J Immunol. 1999 Aug 1;163(3):1696-703.
5
Dysregulated B7-1 and B7-2 expression on nonobese diabetic mouse B cells is associated with increased T cell costimulation and the development of insulitis.非肥胖糖尿病小鼠B细胞上B7-1和B7-2表达失调与T细胞共刺激增加及胰岛炎的发展有关。
J Immunol. 2005 Jan 15;174(2):680-7. doi: 10.4049/jimmunol.174.2.680.
6
IL-4 prevents insulitis and insulin-dependent diabetes mellitus in nonobese diabetic mice by potentiation of regulatory T helper-2 cell function.白细胞介素-4通过增强调节性辅助性T细胞2功能，预防非肥胖糖尿病小鼠的胰岛炎和胰岛素依赖型糖尿病。
J Immunol. 1997 Nov 15;159(10):4686-92.
7
IL-12 administration accelerates autoimmune diabetes in both wild-type and IFN-gamma-deficient nonobese diabetic mice, revealing pathogenic and protective effects of IL-12-induced IFN-gamma.给予白细胞介素-12可加速野生型和γ-干扰素缺陷型非肥胖糖尿病小鼠的自身免疫性糖尿病进程，揭示了白细胞介素-12诱导的γ-干扰素的致病和保护作用。
J Immunol. 2003 Jun 1;170(11):5491-501. doi: 10.4049/jimmunol.170.11.5491.
8
Isolation of self antigen-reactive cells from inflamed islets of nonobese diabetic mice using CD4high expression as a marker.以CD4高表达为标志物，从非肥胖糖尿病小鼠炎症胰岛中分离自身抗原反应性细胞。
J Immunol. 1999 Nov 15;163(10):5708-14.
9
A mechanism for IL-10-mediated diabetes in the nonobese diabetic (NOD) mouse: ICAM-1 deficiency blocks accelerated diabetes.白细胞介素-10介导非肥胖糖尿病（NOD）小鼠糖尿病的机制：细胞间黏附分子-1缺乏可阻断糖尿病的加速发展。
J Immunol. 2000 Dec 15;165(12):7330-7. doi: 10.4049/jimmunol.165.12.7330.
10
The role of lipid antigen presentation, cytokine balance, and major histocompatibility complex in a novel murine model of adoptive transfer of insulitis.脂质抗原呈递、细胞因子平衡和主要组织相容性复合体在胰岛素炎过继转移新型小鼠模型中的作用。
Pancreas. 2000 Mar;20(2):197-205. doi: 10.1097/00006676-200003000-00014.

引用本文的文献

1
A novel sweeping antibody exhibits efficient clearance of the cancer- and autoimmunity-associated cytokine interleukin 16.一种新型的清除性抗体可有效清除与癌症和自身免疫相关的细胞因子白细胞介素16。
bioRxiv. 2025 Aug 1:2025.07.29.666814. doi: 10.1101/2025.07.29.666814.
2
Role of interleukin-16 in human diseases: a novel potential therapeutic target.白细胞介素-16在人类疾病中的作用：一个新的潜在治疗靶点。
Front Immunol. 2025 Jun 2;16:1524026. doi: 10.3389/fimmu.2025.1524026. eCollection 2025.
3
Interleukin-16 is increased in obesity and alters adipogenesis and inflammation .

本文引用的文献

1
CCR2 and CCR5 chemokine receptors differentially influence the development of autoimmune diabetes in the NOD mouse.CCR2 和 CCR5 趋化因子受体对 NOD 小鼠自身免疫性糖尿病的发展有不同影响。
Autoimmunity. 2010 Mar;43(2):156-63. doi: 10.3109/08916930903246464.
2
Relation of circulating concentrations of chemokine receptor CCR5 ligands to C-peptide, proinsulin and HbA1c and disease progression in type 1 diabetes.趋化因子受体CCR5配体的循环浓度与1型糖尿病患者的C肽、胰岛素原、糖化血红蛋白及疾病进展的关系
Clin Immunol. 2008 Jul;128(1):57-65. doi: 10.1016/j.clim.2008.03.458. Epub 2008 Apr 22.
3
Decreased renal ischemia-reperfusion injury by IL-16 inactivation.
白细胞介素-16 在肥胖症中增加，并改变脂肪生成和炎症。
Front Endocrinol (Lausanne). 2024 Mar 13;15:1346317. doi: 10.3389/fendo.2024.1346317. eCollection 2024.
4
hijacks host macrophages-derived interleukin 16 to block phagolysosome maturation for enhancing intracellular growth.劫持宿主巨噬细胞衍生的白细胞介素16以阻止吞噬溶酶体成熟，从而增强细胞内生长。
Emerg Microbes Infect. 2024 Dec;13(1):2322663. doi: 10.1080/22221751.2024.2322663. Epub 2024 Mar 3.
5
Association of IL-16 rs11556218 T/G polymorphism with the risk of developing type 2 diabetes mellitus.白细胞介素-16 rs11556218 T/G多态性与2型糖尿病发生风险的关联
J Diabetes Metab Disord. 2021 Apr 10;20(1):649-653. doi: 10.1007/s40200-021-00795-2. eCollection 2021 Jun.
6
A Novel Resolution of Diabetes: C-C Chemokine Motif Ligand 4 Is a Common Target in Different Types of Diabetes by Protecting Pancreatic Islet Cell and Modulating Inflammation.一种新型糖尿病解决方案：C-C 趋化因子基序配体 4 通过保护胰岛细胞和调节炎症在不同类型糖尿病中是共同的靶点。
Front Immunol. 2021 Apr 23;12:650626. doi: 10.3389/fimmu.2021.650626. eCollection 2021.
7
Subcutaneous transplantation of engineered islet/adipose-derived mesenchymal stem cell sheets in diabetic pigs with total pancreatectomy.工程化胰岛/脂肪来源间充质干细胞片皮下移植于全胰切除的糖尿病猪体内。
Regen Ther. 2021 Jan 13;16:42-52. doi: 10.1016/j.reth.2020.12.005. eCollection 2021 Mar.
8
Faecal microbiota transplantation halts progression of human new-onset type 1 diabetes in a randomised controlled trial.粪便微生物群移植在随机对照试验中阻止了人类新发 1 型糖尿病的进展。
Gut. 2021 Jan;70(1):92-105. doi: 10.1136/gutjnl-2020-322630. Epub 2020 Oct 26.
9
Human Islet Response to Selected Type 1 Diabetes-Associated Bacteria: A Transcriptome-Based Study.人类胰岛对选定的 1 型糖尿病相关细菌的反应：基于转录组的研究。
Front Immunol. 2019 Nov 8;10:2623. doi: 10.3389/fimmu.2019.02623. eCollection 2019.
10
Association of gene polymorphisms with the risk of developing type 2 diabetes mellitus in the Chinese Han population.基因多态性与中国汉族人群 2 型糖尿病发病风险的关联。
Biosci Rep. 2019 Aug 15;39(8). doi: 10.1042/BSR20190821. Print 2019 Aug 30.
通过白细胞介素-16失活减轻肾脏缺血再灌注损伤。
Kidney Int. 2008 Feb;73(3):318-26. doi: 10.1038/sj.ki.5002692. Epub 2007 Nov 14.
4
CCL4 protects from type 1 diabetes by altering islet beta-cell-targeted inflammatory responses.
Diabetes. 2007 Mar;56(3):809-17. doi: 10.2337/db06-0619.
5
The role of liver-derived regulatory dendritic cells in prevention of type 1 diabetes.肝脏来源的调节性树突状细胞在1型糖尿病预防中的作用。
Immunology. 2007 Feb;120(2):251-60. doi: 10.1111/j.1365-2567.2006.02496.x.
6
Production of IL-16 correlates with CD4+ Th1 inflammation and phosphorylation of axonal cytoskeleton in multiple sclerosis lesions.白细胞介素-16的产生与多发性硬化症病变中CD4 + Th1炎症及轴突细胞骨架的磷酸化相关。
J Neuroinflammation. 2006 May 26;3:13. doi: 10.1186/1742-2094-3-13.
7
Transient chemokine receptor blockade does not prevent, but may accelerate type 1 diabetes in prediabetic NOD mice.短暂性趋化因子受体阻断不能预防，但可能加速糖尿病前期非肥胖糖尿病（NOD）小鼠的1型糖尿病发展。
Horm Metab Res. 2006 Mar;38(3):167-71. doi: 10.1055/s-2006-925221.
8
Chemokine receptor CXCR3 desensitization by IL-16/CD4 signaling is dependent on CCR5 and intact membrane cholesterol.白细胞介素-16/CD4信号介导的趋化因子受体CXCR3脱敏作用依赖于CCR5和完整的膜胆固醇。
J Immunol. 2006 Feb 15;176(4):2337-45. doi: 10.4049/jimmunol.176.4.2337.
9
A comprehensive review of interventions in the NOD mouse and implications for translation.对非肥胖糖尿病（NOD）小鼠干预措施的全面综述及其转化意义。
Immunity. 2005 Aug;23(2):115-26. doi: 10.1016/j.immuni.2005.08.002.
10
Anti-IL-16 therapy reduces CD4+ T-cell infiltration and improves paralysis and histopathology of relapsing EAE.抗白细胞介素-16疗法可减少CD4 + T细胞浸润，并改善复发性实验性自身免疫性脑脊髓炎的瘫痪症状和组织病理学表现。
J Neurosci Res. 2005 Mar 1;79(5):680-93. doi: 10.1002/jnr.20377.