1,25-Dihydroxyvitamin D Promotes Negative Feedback Regulation of TLR Signaling Via Targeting MicroRNA-155-SOCS1 in Macrophages

Overview

Journal J Immunol

Specialty Allergy & Immunology

Date 2013 Feb 26

PMID 23436936

Citations 104

Authors

Yunzi Chen

Weicheng Liu

Tao Sun

Yong Huang

Youli Wang

Dilip K Deb

Dosuk Yoon

Juan Kong

Ravi Thadhani

Yan Chun Li

Affiliations

Soon will be listed here.

Abstract

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.

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