@article{3b0a25a8ef2547ca9adbbf9c1f6fdd4a,
title = "Integrin Alpha E (CD103) Limits Virus-Induced IFN-I Production in Conventional Dendritic Cells",
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.",
author = "Vikas Duhan and Vishal Khairnar and Simo Kitanovski and Hamdan, {Thamer A} and Klein, {Andr{\'e}s D} and Judith Lang and Murtaza Ali and Tom Adomati and Hilal Bhat and Sarah-Kim Friedrich and Fanghui Li and Philippe Krebs and Futerman, {Anthony H} and Addo, {Marylyn M} and Cornelia Hardt and Daniel Hoffmann and Lang, {Philipp A} and Lang, {Karl S}",
note = "This study was funded by Deutsche Forschungsgemeinschaft (DFG) grants LA1419/7-1, LA1419/10-1, LA1558/5-1, and 715 SI1558/3-1. This study was further supported by the Sonderforschungsbereich SFB974, the Transregio TRR60, and the Research Training Groups RTG1949/1 and RTG2098, the J{\"u}rgen Manchot Foundation (MOI) and FONDECYT 1180337. Auhtor contributions - VD and VK designed and performed the experiments, analyzed data, and wrote the manuscript. SK executed GWAS and genphen analysis, and wrote and corrected the manuscript. TH performed some in vitro and in vivo experiments and analyzed the data. AK was involved in initiation, analysis, and discussion of GWAS. JL helped for performing FACS sorting and RT-PCR for DC subsets. MA, TA, and HB performed immunohistology for VSV- EBOV, serum IFN ELISA and helped in other assays. S-KF and FL helped for in vitro BMDCs culture experiments. PK was involved in the design of the genetic approach, data discussion and identifying CD103, and corrected the manuscript. AF was involved in data discussion. MMA provided VSV- EBOV vaccine, reviewed the manuscript, and discussed the data. CH was involved in experiment design and data discussion. DH initiated and discussed the GWAS and Genphen study, and wrote and corrected the manuscript. PL discussed the data, study design and the GWAS approach and corrected the manuscript. KL initiated, proposed, and organized the study, wrote, and finalized the manuscript. All authors contributed to the article and approved the submitted version.",
year = "2021",
month = jan,
day = "27",
doi = "10.3389/fimmu.2020.607889",
language = "الإنجليزيّة",
volume = "11",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Media SA",
}