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PBIO SEMINAR SERIES

Location: HSB G-328, 10:30am (unless otherwise noted)

May 22, 2014 - 2013-2014 SEMINAR SERIES

"RIPK1 regulates epithelial homeostasis by inhibiting apoptosis and necroptosis"

Michelle Kelliher, PhD, Professor, UMass Medical School

Host: Chris Liu

Necroptosis has emerged as an important pathway of programmed cell death in implicated in inflammatory and cell death signalling and its kinase activity is believed to drive RIPK3-mediated necroptosis. Here we show that kinaseindependent scaffolding RIPK1 functions to regulate homeostasis and prevent inflammation in barrier tissues by inhibiting epithelial cell apoptosis andnecroptosis. Intestinal epithelial cell-specific RIPK1 ablation sensitized epithelial cells to both apoptosis and necroptosis and caused microbiota-independent intestinal pathology that was prevented by double FADD/RIPK3 deficiency. Epidermis-specific RIPK1 deficiency triggered keratinocyte apoptosis and necroptosis and caused severe skin inflammation that was fully prevented by RIPK3 deficiency. These findings revealed that RIPK1 inhibits RIPK3-mediated necroptosis in keratinocytes in vivo and identified necroptosis as a more potent trigger of inflammation compared to apoptosis. Therefore, RIPK1 is a masterregulator of epithelial cell survival, homeostasis and inflammation in the intestine and the skin.