1,25-dihydroxyvitamin D promotes negative feedback regulation of TLR signaling via targeting microRNA-155-SOCS1 in macrophages

Yunzi Chen, Weicheng Liu, Tao Sun, Yong Huang, Youli Wang, Dilip K. Deb, Dosuk Yoon, Juan Kong, Ravi Thadhani, Yan Chun Li

Research output: Contribution to journalArticle

117 Citations (Scopus)

Abstract

The negative feedbackmechanism is essential tomaintain effective immunity and tissue homeostasis. 1,25-dihydroxyvitamin D (1,25[OH]2D 3) 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.

Original languageEnglish (US)
Pages (from-to)3687-3695
Number of pages9
JournalJournal of Immunology
Volume190
Issue number7
DOIs
StatePublished - Apr 1 2013

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MicroRNAs
Calcitriol Receptors
Macrophages
Innate Immunity
Vitamin D
Down-Regulation
Cytokines
Inflammation
Introns
Immunity
Homeostasis
DNA
Genes
1,25-dihydroxyvitamin D

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

1,25-dihydroxyvitamin D promotes negative feedback regulation of TLR signaling via targeting microRNA-155-SOCS1 in macrophages. / Chen, Yunzi; Liu, Weicheng; Sun, Tao; Huang, Yong; Wang, Youli; Deb, Dilip K.; Yoon, Dosuk; Kong, Juan; Thadhani, Ravi; Li, Yan Chun.

In: Journal of Immunology, Vol. 190, No. 7, 01.04.2013, p. 3687-3695.

Research output: Contribution to journalArticle

Chen, Yunzi ; Liu, Weicheng ; Sun, Tao ; Huang, Yong ; Wang, Youli ; Deb, Dilip K. ; Yoon, Dosuk ; Kong, Juan ; Thadhani, Ravi ; Li, Yan Chun. / 1,25-dihydroxyvitamin D promotes negative feedback regulation of TLR signaling via targeting microRNA-155-SOCS1 in macrophages. In: Journal of Immunology. 2013 ; Vol. 190, No. 7. pp. 3687-3695.
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