| Literature DB >> 33584680 |
Vikas Duhan1,2, Vishal Khairnar1,3, Simo Kitanovski4, Thamer A Hamdan1,5, Andrés D Klein6,7, Judith Lang1, Murtaza Ali1, Tom Adomati1, Hilal Bhat1,8, Sarah-Kim Friedrich1, Fanghui Li1, Philippe Krebs9, Anthony H Futerman6, Marylyn M Addo10,11,12, Cornelia Hardt1, Daniel Hoffmann4, Philipp A Lang13, Karl S Lang1.
Abstract
Early 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.Entities:
Keywords: AKT; CD103; GWAS; IFN-I; Itgae; genome wide association screen; mTOR; vesicular stomatitis virus
Year: 2021 PMID： 33584680 PMCID： PMC7873973 DOI： 10.3389/fimmu.2020.607889
Source DB: PubMed Journal: Front Immunol ISSN： 1664-3224 Impact factor: 7.561