A Novel RIPK1 Inhibitor Reduces GVHD in Mice via a Non-Immunosuppressive Mechanism That Restores Intestinal Homeostasis

Selectively inhibiting RIPK3 in intestinal epithelial cells (IECs) markedly reduces graft-versus-host-disease in murine intestine and liver. IECs RIPK3 cooperates with RIPK1 to trigger MLKL-independent production of T cell-recruiting chemokines and MHC class II molecules which amplify and sustain alloreactive T cell responses.