Deletion of Sufu in macrophages promotes inflammatory responses

Sepsis is a potentially life-threatening condition caused by the body's response to a severe infection. However, the pathogenesis of sepsis remains unclear. Here, we found that Suppressor of Fused (Sufu), a classical negative regulator of Hedgehog signaling, is downregulated in patients with sepsis and in murine peritoneal macrophages treated with lipopolysaccharide (LPS). Deletion of Sufu aggravated LPS-induced lung injury and lethality in mice, and augmented LPS induced proinflammatory gene expression in cultured macrophages. By RNA-seq transcriptome profiling, we identified Sufu as a negative regulator of the TLR-triggered inflammatory response. To study the regulatory mechanism of Sufu in LPS-induced inflammatory signaling, we also performed RNA-seq in PEMs from WT and Sufu-cKO mice 3 hours after LPS challenge.