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

Journal
Frontiers in Immunology
ISSN
1664-3224
Date Issued
2021
Author(s)
Vikas Duhan
Vishal Khairnar
Simo Kitanovski
Thamer A. Hamdan
Judith Lang
Murtaza Ali
Tom Adomati
Hilal Bhat
Sarah-Kim Friedrich
Fanghui Li
Philippe Krebs
Anthony H. Futerman
Marylyn M. Addo
Cornelia Hardt
Daniel Hoffmann
Philipp A. Lang
Karl S. Lang
Type
Resource Types::text::journal::journal article
Scopus ID
2-s2.0-85100828088
WoS ID
WOS:000616529200001
DOI
URL
URL Institutional Repository
Abstract
<jats:p>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 (<jats:italic>Itgae</jats:italic>, 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.</jats:p>
Cite this document
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. Frontiers in Immunology, 11, 607889. https://doi.org/10.3389/fimmu.2020.607889
Subjects
gwas

; 

genome wide association screen

; 

itgae

; 

cd103

; 

vesicular stomatitis virus

; 

ifn-i

; 

akt

; 

mtor

; 

animals

; 

antigens, cd

; 

cells, cultured

; 

dendritic cells

; 

disease models, animal

; 

genome-wide association study

; 

host-pathogen interactions

; 

immunity, innate

; 

integrin alpha chains

; 

interferon type i

; 

mice, 129 strain

; 

mice, inbred akr

; 

mice, inbred balb c

; 

mice, inbred c3h

; 

mice, inbred c57bl

; 

mice, inbred dba

; 

mice, inbred nod

; 

mice, knockout

; 

phosphorylation

; 

proto-oncogene proteins c-akt

; 

receptor, interferon alpha-beta

; 

signal transduction

; 

tor serine-threonine kinases

; 

vesicular stomatitis

; 

vesiculovirus

; 

virus replication

; 

alpha integrin

; 

alpha interferon

; 

alpha2 interferon

; 

beta1 interferon

; 

cd103 antigen

; 

cd11b antigen

; 

cd135 antigen

; 

collagenase

; 

deoxyribonuclease

; 

fc receptor

; 

glutamine

; 

glyceraldehyde 3 phosphate dehydrogenase

; 

immunoglobulin g1

; 

major histocompatibility antigen class 2

; 

mammalian target of rapamycin

; 

mammalian target of rapamycin inhibitor

; 

mercaptoethanol

; 

monoclonal antibody

; 

penicillin derivative

; 

protein kinase b

; 

protein kinase b inhibitor

; 

rapamycin

; 

streptavidin

; 

streptomycin

; 

virus glycoprotein

; 

alpha beta interferon receptor

; 

alpha e integrins

; 

alpha integrin

; 

ifnar1 protein, mouse

; 

interferon

; 

leukocyte antigen

; 

mtor protein, mouse

; 

protein kinase b

; 

target of rapamycin kinase

; 

animal cell

; 

animal model

; 

article

; 

body weight loss

; 

bone marrow derived dendritic cell

; 

cell line

; 

cell suspension

; 

controlled study

; 

death

; 

dendritic cell

; 

enzyme linked immunosorbent assay

; 

fetal bovine serum

; 

flow cytometry

; 

gene expression assay

; 

genome-wide association study

; 

immunofluorescence test

; 

inbred mouse strain

; 

mouse

; 

phenotype

; 

polyacrylamide gel electrophoresis

; 

real time reverse transcription polymerase chain reaction

; 

rna isolation

; 

single nucleotide polymorphism

; 

vero cell line

; 

vesicular stomatitis

; 

vesiculovirus

; 

viral plaque assay

; 

western blotting

; 

129 mouse

; 

akr mouse

; 

animal

; 

bagg albino mouse

; 

c3h mouse

; 

c57bl mouse

; 

cell culture

; 

dba mouse

; 

dendritic cell

; 

disease model

; 

genetics

; 

growth, development and aging

; 

host pathogen interaction

; 

immunology

; 

innate immunity

; 

knockout mouse

; 

metabolism

; 

nonobese diabetic mouse

; 

pathogenicity

; 

phosphorylation

; 

signal transduction

; 

vesiculovirus

; 

virology

; 

virus replication