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

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.

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Duhan, V., Khairnar, V., Kitanovski, S., Hamdan, T.A., Klein, A.D., Lang, J., Ali, M., Adomati, T., Bhat, H., Friedrich, S.-K., Li, F., Krebs, P., Futerman, A.H., Addo, M.M., Hardt, C., Hoffmann, D., Lang, P.A., Lang, K.S., 2021. Integrin Alpha E (CD103) Limits Virus-Induced IFN-I Production in Conventional Dendritic Cells. https://doi.org/10.3389/fimmu.2020.607889
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