Role of microRNA-126 in CD4<sup>+</sup> T cell-mediated autoimmune colitis in mice

Fengyun Chu; Yan Hu; Mengmeng Guo; Chao Chen; Juanjuan Zhao; Yun Liu; Nalin Qin; Jing Zheng; Lin Xu

doi:10.16016/j.1000-5404.201610135

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Role of microRNA-126 in CD4⁺ T cell-mediated autoimmune colitis in mice

更新时间：2026-01-09

- Role of microRNA-126 in CD4⁺ T cell-mediated autoimmune colitis in mice
- Journal of Third Military Medical University Vol. 39, Issue 8, Pages: 767-772(2017)
- 作者机构：
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(31370918);the High-level Innovative Talents Program of Guizhou Province([黔科合人才 (2016)4031号]);the Project of Excellent Young Talents of Zunyi Medical University(15ZY-001)
- DOI：10.16016/j.1000-5404.201610135
  CLC：
- Published：2017-04
- 稿件说明：
移动端阅览
Fengyun Chu, Yan Hu, Mengmeng Guo, et al. Role of microRNA-126 in CD4⁺ T cell-mediated autoimmune colitis in mice[J]. Journal of Third Military Medical University, 2017, 39(8): 767-772.
DOI：

Fengyun Chu, Yan Hu, Mengmeng Guo, et al. Role of microRNA-126 in CD4⁺ T cell-mediated autoimmune colitis in mice[J]. Journal of Third Military Medical University, 2017, 39(8): 767-772. DOI： 10.16016/j.1000-5404.201610135.

摘要

Abstract

Objective

To study the eff

ect of microRNA-126 knockdown on CD4

T cell-mediated autoimmune colitis in mice.

Methods

Wild-type mice and mice with microRNA-126 knockdown (miR-126KD) were fed with dextran sulfate sodium (DSS) solution for 7 d to induce acute autoimmune colitis. The pathological changes of the intestinal tissues were observed with HE staining

and the changes in CD4

T cell percentage and expression levels of CD62L and CD44 molecules in CD4

T cells were analyzed with fluorescence-activated cell sorting (FACS). CD4

CD62L

T cells purified from the spleen of miR-126 KD mice using magnetic activated cell sorting were stained with carboxyfluorescein diacetate

succinimidy1 ester (CFSE) and adoptively transferred into the wild-type mice

which were then exposed to DSS in drinking water to induce autoimmune colitis. The intestinal pathologies and changes of CD62L and CD44 expression in CFSE-positive cells of the recipient mice were analyzed with FACS.

Results

Compared with the normal control mice

miR-126KD mice with DSS-induced acute autoimmune colitis presented with obvious losses of intestinal villi

extensive ulcers in the mucosal epithelium and obvious infiltration of inflammatory cells in the intestinal tissues. FACS results showed that the percentage and total number of CD4

Tcells were increased significantly in miR-126KD mice with a high expression of CD44 and a low expression of CD62L in CD4

T cells (

0.01). Adoptive transfer experiments showed that miR-126KD CD4

T cell transfer aggravated intestinal tissue damage in wild-type mice with acute autoimmune colitis

and CFSE

cells from the wild-type mice showed an increased CD44 expression and a decreased CD62L expression.

Conclusion

miR-126 knockdown aggravates the pathological changes of CD4

Tcell-mediated inflammatory bowel disease in mice induc

ed by DSS.

关键词

Keywords

references

Altwegg R Vincent T TNF blocking therapies and immunomonitoring in patients with inflammatory bowel disease Mediators Inflamm 2014 2014 172821 10.1155/2014/172821 Altwegg R, Vincent T. TNF blocking therapies and immunomonitoring in patients with inflammatory bowel disease[J]. Mediators Inflamm, 2014, 2014:172821.DOI:10.1155/2014/172821.

Huang W M Chang H J Kroeker K I Management of Inflammatory Bowel Disease during Pregnancy and Breastfeeding Varies Widely: A Need for Further Education Can J Gastroenterol Hepatol 2016 2016 6193275 10.1155/2016/6193275 Huang W M, Chang H J, Kroeker K I, et al. Management of Inflammatory Bowel Disease during Pregnancy and Breastfeeding Varies Widely: A Need for Further Education[J]. Can J Gastroenterol Hepatol, 2016, 2016:6193275.DOI:10.1155/2016/6193275.

黄娟魏艳玲王军 294例炎症性肠病临床特点及随访分析第三军医大学学报 2016 38 8 835 839 10.16016/j.1000-5404.201509061.Huang http://aammt.tmmu.edu.cn/oa/DArticle.aspx?type=view&id=201509061 黄娟, 魏艳玲, 王军, 等. 294例炎症性肠病临床特点及随访分析[J].第三军医大学学报, 2016, 38(8): 835-839. DOI:10.16016/j.1000-5404.201509061.Huang

Huang J Wei Y L Wang J Retrospective analysis and follow-up on 294 cases of inflammatory bowel disease J Third Mil Med Univ 2016 38 8 835 839 10.16016/j.1000-5404.201509061 http://aammt.tmmu.edu.cn/oa/DArticle.aspx?type=view&id=201509061 Huang J, Wei Y L, Wang J, et al. Retrospective analysis and follow-up on 294 cases of inflammatory bowel disease[J]. J Third Mil Med Univ, 2016, 38(8): 835-839. DOI:10.16016/j.1000-5404. 201509061.

Zhang Y Yang P Sun T miR-126 and miR-126* repress recruitment of mesenchymal stem cells and inflammatory monocytes to inhibit breast cancer metastasis Nat Cell Biol 2013 15 3 284 294 10.1038/ncb2690 Zhang Y, Yang P, Sun T, et al. miR-126 and miR-126* repress recruitment of mesenchymal stem cells and inflammatory monocytes to inhibit breast cancer metastasis[J]. Nat Cell Biol, 2013, 15(3): 284-294. DOI:10.1038/ncb2690.

Agudo J Ruzo A Tung N The miR-126-VEGFR2 axis controls the innate response to pathogen-associated nucleic acids Nat Immunol 2014 15 1 54 62 10.1038/ni.2767 Agudo J, Ruzo A, Tung N, et al. The miR-126-VEGFR2 axis controls the innate response to pathogen-associated nucleic acids[J]. Nat Immunol, 2014, 15(1): 54-62. DOI:10.1038/ni.2767.

Zhang T Li L Shang Q Circulating miR-126 is a potential biomarker to predict the onset of type 2 diabetes mellitus in susceptible individuals Biochem Biophys Res Commun 2015 463 1-2 60 63 10.1016/j.bbrc.2015.05.017 Zhang T, Li L, Shang Q, et al. Circulating miR-126 is a potential biomarker to predict the onset of type 2 diabetes mellitus in susceptible individuals[J]. Biochem Biophys Res Commun, 2015, 463(1-2): 60-63. DOI:10.1016/j.bbrc.2015.05.017.

Zhao S Wang Y Liang Y MicroRNA-126 regulates DNA methylation in CD4 + T cells and contributes to systemic lupus erythematosus by targeting DNA methyltransferase 1 Arthritis Rheum 2011 63 5 1376 1386 10.1002/art.30196 Zhao S, Wang Y, Liang Y, et al. MicroRNA-126 regulates DNA methylation in CD4 + T cells and contributes to systemic lupus erythematosus by targeting DNA methyltransferase 1[J ] . Arthritis Rheum, 2011, 63(5): 1376-1386. DOI: 10.1002/art.30196.

Okuyama K Ikawa T Gentner B MicroRNA-126-mediated control of cell fate in B-cell myeloid progenitors as a potential alternative to transcriptional factors Proc Natl Acad Sci USA 2013 110 33 13410 13415 10.1073/pnas.1220710110 Okuyama K, Ikawa T, Gentner B, et al. MicroRNA-126-mediated control of cell fate in B-cell myeloid progenitors as a potential alternative to transcriptional factors[J]. Proc Natl Acad Sci USA, 2013, 110(33): 13410-13415. DOI:10.1073/pnas.1220710110.

Goerke S M Kiefer L S Stark G B miR-126 modulates angiogenic growth parameters of peripheral blood endothelial progenitor cells Biol Chem 2015 396 3 245 252 10.1515/hsz-2014-0259 Goerke S M, Kiefer L S, Stark G B, et al. miR-126 modulates angiogenic growth parameters of peripheral blood endothelial progenitor cells[J]. Biol Chem, 2015, 396(3): 245-252. DOI:10.1515/hsz-2014-0259.

胡燕廖珍媛李永菊真核表达载体pEGFP-C2-miR-126-sponge的构建及其表达活性研究第三军医大学学报 2014 36 1 33 37 10.16016/j.1000-5404.2014.01.016 http://aammt.tmmu.edu.cn/oa/DArticle.aspx?type=view&id=201306116 胡燕, 廖珍媛, 李永菊, 等.真核表达载体pEGFP-C2-miR-126-sponge的构建及其表达活性研究[J].第三军医大学学报, 2014, 36(1): 33-37. DOI: 10.16016/j.1000-5404.2014.01.016.

Hu Y Liao Z Y Li Y J Construction of pEGFP-c2-mir-126-sponge eukaryotic expression vector and its expression activity J Third Mil Med Univ 2014 36 1 33 37 10.16016/j.1000-5404.2014.01.016 http://aammt.tmmu.edu.cn/oa/DArticle.aspx?type=view&id=201306116 Hu Y, Liao Z Y, Li Y J, et al. Construction of pEGFP-c2-mir-126-sponge eukaryotic expression vector and its expression activity[J]. J Third Mil Med Univ, 2014, 36(1): 33-37. DOI: 10.16016/j.1000-5404. 2014.01.016.

胡燕李永菊陈超 microRNA-126基因敲减小鼠的鉴定及其血糖水平变化中南大学学报 (医学版) 2015 40 1 12 17 10.11817/j.issn.1672-7347.2015.01.003 胡燕, 李永菊, 陈超, 等. microRNA-126基因敲减小鼠的鉴定及其血糖水平变化[J].中南大学学报 (医学版), 2015, 40(1): 12-17. DOI:10.11817/j.issn.1672-7347.2015.01.003.

Hu Y Li Y J Chen C Identification of miR-126 knockdown mouse and the change of blood glucose Journal of Central South University (Medical Science) 2015 40 1 12 17 10.11817/j.issn.1672-7347.2015.01.003 Hu Y, Li Y J, Chen C, et al. Identification of miR-126 knockdown mouse and the change of blood glucose[J]. Journal of Central South University (Medical Science), 2015, 40(1): 12-17. DOI: 10.11817/j.issn.1672-7347. 2015.01.003.

Kalla R Ventham N T Kennedy N A MicroRNAs: new players in IBD Gut 2015 64 3 504 517 10.1136/gutjnl-2014-307891 Kalla R, Ventham N T, Kennedy N A, et al. MicroRNAs: new players in IBD[J]. Gut, 2015, 64(3): 504-517. DOI:10.1136/gutjnl-2014-307891.

Maoa R Zou F Yang L The loss of MiR-139-5p promotes colitis-associated tumorigenesis by mediating PI3K/AKT/Wnt signaling Int J Biochem Cell Biol 2015 69 153 161 10.1016/j.biocel.2015.10.008 Maoa R, Zou F, Yang L, et al. The loss of MiR-139-5p promotes colitis-associated tumorigenesis by mediating PI3K/AKT/Wnt signaling[J]. Int J Biochem Cell Biol, 2015, 69: 153-161.DOI:10.1016/j.biocel.2015.10.008.

Runtsch M C Hu R Alexander M MicroRNA-146a constrains multiple parameters of intestinal immunity and increases susceptibility to DSS colitis Oncotarget 2015 6 30 28556 28572 10.18632/oncotarget.5597 Runtsch M C, Hu R, Alexander M, et al. MicroRNA-146a constrains multiple parameters of intestinal immunity and increases susceptibility to DSS colitis[J]. Oncotarget, 2015, 6(30): 28556-28572. DOI: 10. 18632/oncotarget.5597.

Paraskevi A Theodoropoulos G Papaconstantinou I Circulating MicroRNA in inflammatory bowel disease J Crohns Colitis 2012 6 9 900 904 10.1016/j.crohns.2012.02.006 Paraskevi A, Theodoropoulos G, Papaconstantinou I, et al. Circulating MicroRNA in inflammatory bowel disease[J]. J Crohns Colitis, 2012, 6(9): 900-904.DOI:10.1016/j.crohns.2012.02.006.

Wei Xu Ch en Li Hua Implication of miRNAs for inflammatory bowel disease treatment:Systematic review World J Gastrointest Pathophysiol 2014 5 2 63 70 10.4291/wjgp.v5.i2.63 Wei Xu, Chen, Li Hua, et al. Implication of miRNAs for inflammatory bowel disease treatment:Systematic review[J]. World J Gastrointest Pathophysiol, 2014, 5(2): 63-70. DOI: 10.4291/wjgp.v5.i2.63.

He C Shi Y Wu R miR-301a promotes intestinal mucosal inflammation through induction of IL-17A and TNF-α in IBD Gut 2016 65 12 1938 1950 10.1136/gutjnl-2015-309389 He C, Shi Y, Wu R, et al. miR-301a promotes intestinal mucosal inflammation through induction of IL-17A and TNF-α in IBD[J]. Gut, 2016, 65(12): 1938-1950. DOI: 10.1136/gutjnl-2015-309389.

Feng X Wang H Ye S Up-regulation of microRNA-126 may contribute to pathogenesis of ulcerative colitis via regulating NF-kappaB inhibitor IκBα PLoS ONE 2012 7 12 e52782 10.1371/journal.pone.0052782 Feng X, Wang H, Ye S, et al. Up-regulation of microRNA-126 may contribute to pathogenesis of ulcerative colitis via regulating NF-kappaB inhibitor IκBα[J]. PLoS ONE, 2012, 7(12): e52782.DOI:10.1371/journal.pone.0052782.

Bregenholt S , Reimann J , Claesson M H . Proliferation and apoptosis of lamina propria CD4 + T cells from scid mice with inflammatory bowel disease [J ] . Eur J Immunol , 1998 , 28 ( 11 ): 3655 - 3663 . DOI: 10.1002/(SICI)1521-4141(199811)28:11<3655::AID-IMMU3655>3.0.CO; 2-9 . Bregenholt S, Reimann J, Claesson M H. Proliferation and apoptosis of lamina propria CD4 + T cells from scid mice with inflammatory bowel disease[J ] . Eur J Immunol, 1998, 28(11): 3655-3663. DOI: 10.1002/(SICI)1521-4141(199811)28:11 < 3655::AID-IMMU3655 > 3.0.CO; 2-9.

蒲爱民张治草韩宾姜黄素通过调节肠道IEL亚群缓解DSS诱导的小鼠溃疡性结肠炎第三军医大学学报 2016 38 11 1276 1280 10.16016/j.1000-5404.201511154 http://aammt.tmmu.edu.cn/oa/DArticle.aspx?type=view&id=201511154 蒲爱民, 张治草, 韩宾, 等.姜黄素通过调节肠道IEL亚群缓解DSS诱导的小鼠溃疡性结肠炎[J].第三军医大学学报, 2016, 38(11): 1276-1280. DOI: 10.16016/j.1000-5404.201511154.

Pu A M Zhang Z C Han B Curcumin alleviates DSS-induced colonic inflammation by regulating intestinal IEL subsets in mice J Third Mil Med Univ 2016 38 11 1276 1280 10.16016/j.1000-5404.201511154 http://aammt.tmmu.edu.cn/oa/DArticle.aspx?type=view&id=201511154 Pu A M, Zhang Z C, Han B, et al. Curcumin alleviates DSS-induced colonic inflammation by regulating intestinal IEL subsets in mice[J]. J Third Mil Med Univ, 2016, 38(11): 1276-1280. DOI: 10.16016/j.1000-5404.201511154.

Dotan I Allez M Nakazawa A Intestinal epithelial cells from inflammatory bowel disease patients preferentially stimulate CD4 + T cells to proliferate and secrete interferon-gamma Am J Physiol Gastrointest Liver Physiol 2007 292 6 G1630 G1640 10.1152/ajpgi.00294.2006 Dotan I, Allez M, Nakazawa A, et al. Intestinal epithelial cells from inflammatory bowel disease patients preferentially stimulate CD4 + T cells to proliferate and secrete interferon-gamma[J ] . Am J Physiol Gastrointest Liver Physiol, 2007, 292(6):G1630-G1640.DOI:10.1152/ajpgi.00294.2006.

Holmkvist P Pool L H gerbrand K IL-18 Rα-deficient CD4(+) T cells induce intestinal inflammation in the CD45RB (hi) transfer model of colitis despite impaired innate responsiveness Eur J Immunol 2016 46 6 1371 1382 10.1002/eji.201545957 Holmkvist P, Pool L, H gerbrand K, et al. IL-18 Rα-deficient CD4(+) T cells induce intestinal inflammation in the CD45RB (hi) transfer model of colitis despite impaired innate responsiveness[J]. Eur J Immunol, 2016, 46(6): 1371-1382. DOI: 10.1002/eji.201545957.

崔盼盼胡燕陶弋婧 miR-126敲减增强小鼠CD4 + T细胞体内活性并促进其向Th1细胞分化细胞与分子免疫学杂志 2016 32 3 347 351 http://www.cqvip.com/QK/94263X/201603/668126787.html 崔盼盼, 胡燕, 陶弋婧, 等. miR-126敲减增强小鼠CD4 + T细胞体内活性并促进其向Th1细胞分化[J ] .细胞与分子免疫学杂志, 2016, 32(3): 347-351.

Cui P P Hu Y Tao Y J MiR-126 knockdown enhances the activity of murine CD4 + T cells in vivo and promotes their differentiation into Th1 cells Chinese Journal of Cellular and Molecular Immunology 2016 32 3 347 351 http://www.cqvip.com/QK/94263X/201603/668126787.html Cui P P, Hu Y, Tao Y J, et al. MiR-126 knockdown enhances the activity of murine CD4 + T cells in vivo and promotes their differentiation into Th1 cells[J ] . Chinese Journal of Cellular and Molecular Immunology, 2016, 32(3): 347-351.

Hosokawa K Muranski P Feng X Identification of novel microRNA signatures linked to acquired aplastic anemia Haematologica 2015 100 12 1534 1545 10.3324/haematol.2015.126128 Hosokawa K, Muranski P, Feng X, et al. Identification of novel microRNA signatures linked to acquired aplastic anemia[J]. Haematologica, 2015, 100(12): 1534-1545. DOI: 10.3324/haematol.2015.126128.

Mattes J Collison A Plank M Antagonism of microRNA-126 suppresses the effector function of TH2 cells and the development of allergic airways disease Proc Natl Acad Sci USA 2009 106 44 18704 18709 10.1073/pnas.0905063106 Mattes J, Collison A, Plank M, et al. Antagonism of microRNA-126 suppresses the effector function of TH2 cells and the development of allergic airways disease[J]. Proc Natl Acad Sci USA, 2009, 106(44):18704-18709. DOI: 10.1073/pnas.0905063106.

Qin A Wen Z Zhou Y MicroRNA-126 regulates the induction and function of CD4(+) Foxp3(+) regulatory T cells through PI3K/AKT pathway J Cell Mol Med 2013 17 2 252 264 10.1111/jcmm.12003 Qin A, Wen Z, Zhou Y, et al. MicroRNA-126 regulates the induction and function of CD4(+) Foxp3(+) regulatory T cells through PI3K/AKT pathway[J]. J Cell Mol Med, 2013, 17(2): 252-264. DOI: 10.1111/jcmm.12003.

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Role of microRNA-126 in CD4+ T cell-mediated autoimmune colitis in mice

DOI：10.16016/j.1000-5404.201610135

摘要

Abstract

关键词

Keywords

references

Role of microRNA-126 in CD4⁺ T cell-mediated autoimmune colitis in mice