Integrin Alpha E (CD103) Limits Virus-Induced IFN-I Production in Conventional Dendritic Cells

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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.

Description

Centro de Genética y Genómica (ICIM)

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Citation

Duhan V, Khairnar V, Kitanovski S, Hamdan TA, Klein AD, Lang J, Ali M, Adomati T, Bhat H, Friedrich SK, Li F, Krebs P, Futerman AH, Addo MM, Hardt C, Hoffmann D, Lang PA, Lang KS. Integrin Alpha E (CD103) Limits Virus-Induced IFN-I Production in Conventional Dendritic Cells. Front Immunol. 2021 Jan 27;11:607889. doi: 10.3389/fimmu.2020.607889. PMID: 33584680; PMCID: PMC7873973

Keywords

KT, CD103, GWAS, IFN-I, Itgae, Genome wide association screen, mTOR, Vesicular stomatitis virus

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