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

Brain, O. et al. (2013) The intracellular sensor NOD2 induces microRNA-29 expression in human dendritic cells to limit IL-23 release. Immunity, 39(3), pp. 521-536. (doi: 10.1016/j.immuni.2013.08.035) (PMID:24054330)

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Abstract

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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Maloy, Professor Kevin
Authors: Brain, O., Owens, B. M.J., Pichulik, T., Allan, P., Khatamzas, E., Leslie, A., Steevels, T., Sharma, S., Mayer, A., Catuneanu, A. M., Morton, V., Sun, M.-Y., Jewell, D., Coccia, M., Harrison, O., Maloy, K., Schönefeldt, S., Bornschein, S., Liston, A., and Simmons, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Immunity
Publisher:Elsevier (Cell Press)
ISSN:1074-7613
ISSN (Online):1097-4180

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