Research ArticleGraft-Versus-Host Disease

RIG-I/MAVS and STING signaling promote gut integrity during irradiation- and immune-mediated tissue injury

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Science Translational Medicine  19 Apr 2017:
Vol. 9, Issue 386, eaag2513
DOI: 10.1126/scitranslmed.aag2513

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A STING in the tail for GVHD

RIG-I/MAVS and cGAS/STING are innate recognition pathways that sense specific RNA or DNA patterns and induce IFN-I expression. Fischer et al. now show that endogenous and targeted activation of these pathways reduces intestinal injury after irradiation or chemotherapy and during graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Activation of RIG-I/MAVS and STING results in an IFN-I response that protects intestinal mucosal barrier function in vivo and promotes growth of intestinal organoids in vitro. IFN-I–mediated promotion of gut integrity correlates with attenuated graft-versus-host disease. Targeting these pathways may allow amelioration of intestinal tissue injury and regeneration of the intestinal stem cell niche.