The Intracellular Sensor NOD2 Induces MicroRNA-29 Expression in Human Dendritic Cells to Limit IL-23 Release

被引：195

作者：

Brain, Oliver ^{[1
,2
]}

Owens, Benjamin M. J. ^{[1
]}

Pichulik, Tica ^{[2
]}

Allan, Philip ^{[1
,2
]}

Khatamzas, Elham ^{[2
]}

Leslie, Alasdair ^{[2
]}

Steevels, Tessa ^{[1
,2
]}

Sharma, Sameer ^{[1
,2
]}

Mayer, Alice ^{[2
]}

Catuneanu, Ana Maria ^{[1
,2
]}

Morton, Victoria ^{[1
,2
]}

Sun, Mei-Yi ^{[2
]}

Jewell, Derek ^{[1
]}

Coccia, Margherita ^{[3
]}

Harrison, Oliver ^{[3
]}

Maloy, Kevin ^{[3
]}

Schoenefeldt, Susann ^{[4
,5
]}

Bornschein, Simon ^{[4
,5
]}

Liston, Adrian ^{[4
,5
]}

Simmons, Alison ^{[1
,2
]}

机构：

[1] Univ Oxford, John Radcliffe Hosp, Translat Gastroenterol Unit, Oxford OX3 9DS, England

[2] Univ Oxford, Weatherall Inst Mol Med, Human Immunol Unit, Oxford OX3 9DS, England

[3] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England

[4] VIB, Autoimmune Genet Lab, B-3000 Louvain, Belgium

[5] Univ Louvain, Dept Microbiol & Immunol, B-3000 Louvain, Belgium

来源：

IMMUNITY | 2013年 / 39卷 / 03期

基金：

英国医学研究理事会; 美国国家卫生研究院; 欧洲研究理事会; 英国惠康基金;

关键词：

INFLAMMATORY-BOWEL-DISEASE; INNATE IMMUNE-RESPONSES; HUMAN MONOCYTIC CELLS; HELPER T-CELLS; NF-KAPPA-B; CROHNS-DISEASE; ESCHERICHIA-COLI; INTESTINAL INFLAMMATION; INTERFERON-GAMMA; LYMPHOID-CELLS;

D O I：

10.1016/j.immuni.2013.08.035

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

NOD2 is an intracellular sensor that contributes to immune defense and inflammation. Here we investigated whether NOD2 mediates its effects through control of microRNAs (miRNAs). miR-29 expression was upregulated in human dendritic cells (DCs) in response to NOD2 signals, and miR-29 regulated the expression of multiple immune mediators. In particular, miR-29 downregulated interleukin-23 (IL-23) by targeting IL-12p40 directly and IL-23p19 indirectly, likely via reduction of ATF2. DSS-induced colitis was worse in miR-29-deficient mice and was associated with elevated IL-23 and T helper 17 signature cytokines in the intestinal mucosa. Crohn's disease (CD) patient DCs expressing NOD2 polymorphisms failed to induce miR-29 upon pattern recognition receptor stimulation and showed enhanced release of IL-12p40 on exposure to adherent invasive E. coli. Therefore, we suggest that loss of miR-29-mediated immunoregulation in CD DCs might contribute to elevated IL-23 in this disease.

引用

页码：521 / 536

页数：16

共 54 条

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Interleukin-23 Drives Intestinal Inflammation through Direct Activity on T Cells [J].