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

C-type lectins serve multiple functions through recognizing carbohydrate ch ains. Here we report a novel C-type lectin, macrophage-inducible C-type lec tin (Mincle), as a downstream target of NF-IL6 in macrophages, NF-IL6 belon gs to the CCAAT/enhancer binding protein (C/EBP) of transcription factors a nd plays a crucial role in activated macrophages, However, what particular genes are regulated by NF-IL6 has been poorly defined in macrophages. Ident ification 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 periton eal macrophages and isolated Mincle that exhibits the highest homology to t he members of group II C-type lectins, Mincle mRNA expression was strongly induced in response to several inflammatory stimuli,: such as LPS, TNF-alph a, IL-6, and IFN-gamma in wild-type macrophages, In contrast, NF-IL6-defici ent macrophages displayed a much lower level of Mincle mRNA induction follo wing treatment with these inflammatory reagents. The mouse Mincle proximal promoter region contains an indispensable NF-IL6 binding element, demonstra ting that Mincle is a direct target of NF-IL6, The Mincle gene locus was ma pped at 0.6 centiMorgans proximal to CD4 on mouse chromosome 6.