Butyrate-induced LncRNA lncly6c promotes Ly6Chigh to Ly6Clow/neg macrophages through lncly6c /C/EBP/Nr4A-1 axis

Gut macrophages play a critical role in maintaining the homeostasis of gut immunes. The inflammatory macrophages generally are differentiated into resident macrophages to realize their function in gut tissues. But it is unclear how these inflammatory macrophages to differentiate resident macrophages. We here found that lycLy6c, a novel ultraconserved lncRNA, may promote the differentiation of gut inflammatory macrophage into gut resident macrophages. We demonstrate gut microbiota metabolites butyrate may upregulate the expression of lncly6c. Lncly6c not only binds with transcription factor C/EBPβ but also binds with multiple components of enzyme complexes, which promote the accumulation of H3K4me3 markers on the promoter region of NrA4-1. As a result, lncly6c causes the upregulation of Nr4A-1 to promote inflammatory macrophage to differentiate the resident macrophages. These results not only offer an evidence for gut microbiota to maintaining the gut homeostasis but also suggest a potential target for the therapy for colitis-associated diseases. 10 × Genomics scRNA-seq was performed To further understand the effects of lncly6c on the differentiation of macrophages.