Interferon regulated genes in mouse intestine after irradiation and prophylactic Rig-I activation

As RIG-I activation induces potent IFN-I responses,we analyzed the role of IFN-I in intestinal tissue protection and prevention of GVHD. We performed RNA sequencing with tissue samples from SI of WT mice that received TBI -/+ previous 3pRNA treatment and -/+ antibody-mediated blockade of IFNAR. Application of 3pRNA before TBI resulted in a significant increase of IFN-inducible genes in the SI as compared to solely irradiated mice. Blockade of IFNAR signaling abrogated 3pRNA-mediated up-regulation of IFN-induced genes, demonstrating that RIG-I-induced gene-regulation depends on IFN-I. Overall design: Balb/c mice were solely irradiated (9Gy) (n=3), pretreated with Rig-I agonist 3pRNA prior (d-1) to irradiation (n=3) or pre-treated with 3pRNA (d-1) + anti-IFNaR1 blocking antibody (d-2) prior to irradiation (n=3). RNA from small intestines was isolated 12h after irradiation and used for RNA sequencing.

45

Fischer JC, Bscheider M, Eisenkolb G, Lin CC, Wintges A, Otten V, Lindemans CA, Heidegger S, Rudelius M, Monette S, Porosnicu Rodriguez KA, Calafiore M, Liebermann S, Liu C, Lienenklaus S, Weiss S, Kalinke U, Ruland J, Peschel C, Shono Y, Docampo M, Velardi E, Jenq RR, Hanash AM, Dudakov JA, Haas T, van den Brink MRM, Poeck H