Cai, Zhijian

Bone marrow‐derived macrophages (BMMs) treated with granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) or macrophage colony‐stimulating factor (M‐CSF), differentiate into GM‐CSF‐induced mouse bone marrow‐derived macrophages (GM‐BMMs) or M‐CSF‐induced mouse bone marrow‐derived macrophages (M‐BMMs), which have an M1 or M2 profile, respectively. GM‐BMMs produce large amounts of proinflammatory cytokines and mediate resistance to pathogens, whereas M‐BMMs produce antiinflammatory cytokines that contribute to tissue repair and remodeling. M‐BMMs stimulated with lipopolysaccharide (LPS) are in an antiinflammatory state, with an IL‐12lowIL‐10high phenotype. However, the regulation of this process remains unclear. Klf10 belongs to the family of Krüppel‐like transcription factors and was initially described as a TGF‐β inducible early gene 1. IL‐12p40 is upregulated in LPS‐stimulated M‐BMMs from Klf10‐deficient mice, but downregulated during Klf10 overexpression. Klf11, another member of the Krüppel‐like factor family, can also repress the production of IL‐12p40. Furthermore, Klf10 binds to the CACCC element of the IL‐12p40 promoter and inhibits its transcription. We have therefore identified Klf10 as a transcription factor that regulates the expression of IL‐12p40 in M‐BMMs.