Duhan, VikasVikasDuhanKhairnar, VishalVishalKhairnarKitanovski, SimoSimoKitanovskiHamdan, Thamer AThamer AHamdanKlein, Andrés DAndrés DKleinLang, JudithJudithLangAli, MurtazaMurtazaAliAdomati, TomTomAdomatiBhat, HilalHilalBhatFriedrich, Sarah-KimSarah-KimFriedrichLi, FanghuiFanghuiLiKrebs, PhilippePhilippeKrebs0000-0003-4918-6654Futerman, Anthony HAnthony HFutermanAddo, Marylyn MMarylyn MAddoHardt, CorneliaCorneliaHardtHoffmann, DanielDanielHoffmannLang, Philipp APhilipp ALangLang, Karl SKarl SLang2024-09-022024-09-022021https://boris-portal.unibe.ch/handle/20.500.12422/40093Early and strong production of IFN-I by dendritic cells is important to control vesicular stomatitis virus (VSV), however mechanisms which explain this cell-type specific innate immune activation remain to be defined. Here, using a genome wide association study (GWAS), we identified Integrin alpha-E (Itgae, CD103) as a new regulator of antiviral IFN-I production in a mouse model of vesicular stomatitis virus (VSV) infection. CD103 was specifically expressed by splenic conventional dendritic cells (cDCs) and limited IFN-I production in these cells during VSV infection. Mechanistically, CD103 suppressed AKT phosphorylation and mTOR activation in DCs. Deficiency in CD103 accelerated early IFN-I in cDCs and prevented death in VSV infected animals. In conclusion, CD103 participates in regulation of cDC specific IFN-I induction and thereby influences immune activation after VSV infection.enAKT CD103 GWAS IFN-I Itgae genome wide association screen mTOR vesicular stomatitis virus500 - Science::570 - Life sciences; biologyarticle10.48350/1522573358468010.3389/fimmu.2020.607889