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Integrin CD11b positively regulates TLR4-induced signalling pathways in dendritic cells but not in macrophages

Title: Integrin CD11b positively regulates TLR4-induced signalling pathways in dendritic cells but not in macrophages
Authors: Ling, GS
Bennett, J
Woollard, KJ
Szajna, M
Fossati-Jimack, L
Taylor, PR
Scott, D
Franzoso, G
Cook, HT
Botto, M
Item Type: Journal Article
Abstract: Tuned and distinct responses of macrophages and dendritic cells to Toll-like receptor 4 (TLR4) activation induced by lipopolysaccharide (LPS) underpin the balance between innate and adaptive immunity. However, the molecule(s) that confer these cell-type-specific LPS-induced effects remain poorly understood. Here we report that the integrin αM (CD11b) positively regulates LPS-induced signalling pathways selectively in myeloid dendritic cells but not in macrophages. In dendritic cells, which express lower levels of CD14 and TLR4 than macrophages, CD11b promotes MyD88-dependent and MyD88-independent signalling pathways. In particular, in dendritic cells CD11b facilitates LPS-induced TLR4 endocytosis and is required for the subsequent signalling in the endosomes. Consistent with this, CD11b deficiency dampens dendritic cell-mediated TLR4-triggered responses in vivo leading to impaired T-cell activation. Thus, by modulating the trafficking and signalling functions of TLR4 in a cell-type-specific manner CD11b fine tunes the balance between adaptive and innate immune responses initiated by LPS.
Issue Date: 15-Jan-2014
Date of Acceptance: 2-Dec-2013
URI: http://hdl.handle.net/10044/1/40998
DOI: http://dx.doi.org/10.1038/ncomms4039
ISSN: 2041-1723
Publisher: Nature Publishing Group
Journal / Book Title: Nature Communications
Volume: 5
Copyright Statement: This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. To view a copy of this licence visit http://creativecommons.org/licenses/by/3.0/.
Sponsor/Funder: Cancer Research UK
Funder's Grant Number: C26587/A15115
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
IN-VIVO
RECEPTOR 4
T-CELLS
KAPPA-B
LIPOPOLYSACCHARIDE
ACTIVATION
INDUCTION
TOLERANCE
RESPONSES
MAC-1
Adaptive Immunity
Animals
Antigens, CD11b
Cells, Cultured
Chemokine CCL5
Cytokines
Dendritic Cells
Female
Immunity, Innate
Lipopolysaccharides
Macrophages
Mice
Mice, Inbred C57BL
Mice, Knockout
Myeloid Differentiation Factor 88
Signal Transduction
Toll-Like Receptor 4
MD Multidisciplinary
Publication Status: Published
Article Number: 3039
Appears in Collections:Department of Medicine
Faculty of Medicine



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