Huang et al. demonstrated that epithelial-specific knockout of S1PP2 in mice led to milder colitis, lower levels of TNF-α, IL-6 and IL-1β, and higher mucosal integrity than that in WT mice after DSS induction, suggesting the protective effect of epithelial S1P on the intestinal mucosal barrier under acute colitis (Huang et al., 2016). Here, TNF is linked to colitis.