A novel LPS-inducible C-type lectin is a transcriptional target of NF- IL6 in macrophages

Makoto Matsumoto, Takashi Tanaka, Tsuneyasu Kaisho, Hideki Sanjo, Neal G. Copeland, Debra J. Gilbert, Nancy A. Jenkins, Shizuo Akira

Research output: Contribution to journalArticle

200 Scopus citations

Abstract

C-type lectins serve multiple functions through recognizing carbohydrate chains. Here we report a novel C-type lectin, macrophage-inducible C-type lectin (Mincle), as a downstream target of NF-IL6 in macrophages. NF-IL6 belongs to the CCAAT/enhancer binding protein (C/EBP) of transcription factors and plays a crucial role in activated macrophages. However, what particular genes are regulated by NF-IL6 has been poorly defined in macrophages. Identification of downstream targets is required to elucidate the function of NF-IL6 in more detail. To identify downstream genes of NF- IL6, we screened a subtraction library constructed from wild-type and NF-IL6- deficient peritoneal macrophages and isolated Mincle that exhibits the highest homology to the members of group II C-type lectins. Mincle mRNA expression was strongly induced in response to several inflammatory stimuli, such as LPS, TNF-α, IL-6, and IFN-γ in wild-type macrophages. In contrast, NF-IL6-deficient macrophages displayed a much lower level of Mincle mRNA induction following treatment with these inflammatory reagents. The mouse Mincle proximal promoter region contains an indispensable NF-IL6 binding element, demonstrating that Mincle is a direct target of NF-IL6. The Mincle gene locus was mapped at 0.6 centiMorgans proximal to CD4 on mouse chromosome 6.

Original languageEnglish (US)
Pages (from-to)5039-5048
Number of pages10
JournalJournal of Immunology
Volume163
Issue number9
StatePublished - 1999

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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