The intracellular sensor NOD2 induces microRNA-29 expression in human dendritic cells to limit IL-23 release.

Journal article

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.

Authors: Brain, O; Owens, B; Pichulik, T; Allan, P; Khatamzas, E

• Publication status: Published
• Journal: Immunity
• Volume: 39
• Issue: 3
• Pages: 521-536
• Publication date: 2013-09-01
• DOI: 10.1016/j.immuni.2013.08.035
• EISSN: 1097-4180
• ISSN: 1074-7613
• Language: English
• Keywords: MicroRNAs; Interleukin-23; Nod2 Signaling Adaptor Protein; Crohn Disease; Cells, Cultured; Dendritic Cells; Interleukin-12 Subunit p40; Escherichia coli Infections; Polymorphism, Single Nucleotide; Th17 Cells; Activating Transcription Factor 2; Mice; Humans; Mice, Knockout; Animals; Escherichia coli; Inflammation; Intestinal Mucosa