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

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• 作者：Oliver Brain ; Benjamin?M.J. Owens ; Tica Pichulik ; Philip Allan ; Elham Khatamzas ; Alasdair Leslie ; Tessa Steevels ; Sameer Sharma ; Alice Mayer ; Ana?Maria Catuneanu ; Victoria Morton ; Mei-Yi Sun ; Derek Jewell ; Margherita Coccia ; Oliver Harrison ; Kevin Maloy ; Susann Sch?nefeldt ; Simon Bornschein ; Adrian Liston ; Alison Simmons ; et al.
• 刊名：Immunity
• 出版年：2013
• 出版时间：19 September, 2013
• 年：2013
• 卷：39
• 期：3
• 页码：521-536
• 全文大小：3071 K

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Summary

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.