IL-10 constrains sphingolipid metabolism to limit inflammation

Abstract Interleukin-10 (IL-10) is a key anti-inflammatory cytokine that can limit immune cell activation and cytokine production in innate immune cell types 1 . Loss of IL-10 signalling results in life-threatening inflammatory bowel disease in humans and mice—however, the exact mechanism by which IL-10 signalling subdues inflammation remains unclear 2–5 . Here we find that increased saturated very long chain (VLC) ceramides are critical for the heightened inflammatory gene expression that is a hallmark of IL-10 deficiency. Accordingly, genetic deletion of ceramide synthase 2 (encoded by Cers2 ), the enzyme responsible for VLC ceramide production, limited the exacerbated inflammatory gene expression programme…

• NS
  National Science Foundation
• HH
  Howard Hughes Medical Institute
• CR
  Cancer Research Institute
• YU
  Yale University
• NI
  National Institutes of Health

  Awards: DK007356, 1S10OD030363-01A1
• NI
  National Institute of General Medical Sciences

  Award: 1S10OD030363-01A1