The negative feedback mechanism is essential to maintain effective immunity and tissue homeostasis. 1,25-dihydroxyvitamin D (1,25[OH]2D3) modulates innate immune response, but the mechanism remains poorly understood. In this article, we report that vitamin D receptor signaling attenuates TLR-mediated inflammation by enhancing the negative feedback inhibition. Vitamin D receptor inactivation leads to hyperinflammatory response in mice and macrophage cultures when challenged with LPS, because of microRNA-155 (miR-155) overproduction that excessively suppresses suppressor of cytokine signaling 1, a key regulator that enhances the negative feedback loop. Deletion of miR-155 attenuates vitamin D suppression of LPS-induced inflammation, confirming that 1,25(OH)2D3 stimulates suppressor of cytokine signaling 1 by downregulating miR-155. 1,25(OH)2D3 downregulates bic transcription by inhibiting NF-κB activation, which is mediated by a κB cis-DNA element located within the first intron of the bic gene. Together, these data identify a novel regulatory mechanism for vitamin D to control innate immunity.
CITATION STYLE
Chen, Y., Liu, W., Sun, T., Huang, Y., Wang, Y., Deb, D. K., … Li, Y. C. (2013). 1,25-Dihydroxyvitamin D Promotes Negative Feedback Regulation of TLR Signaling via Targeting MicroRNA-155–SOCS1 in Macrophages. The Journal of Immunology, 190(7), 3687–3695. https://doi.org/10.4049/jimmunol.1203273
Mendeley helps you to discover research relevant for your work.