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

Ling, Guang Sheng, Bennett, Jason, Woollard, Kevin J., Szajna, Marta, Fossati-Jimack, Liliane, Taylor, Philip R. ORCID: https://orcid.org/0000-0003-0163-1421, Scott, Diane, Franzoso, Guido, Cook, H. Terence and Botto, Marina 2014. Integrin CD11b positively regulates TLR4-induced signalling pathways in dendritic cells but not in macrophages. Nature Communications 5 , 3039. 10.1038/ncomms4039

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Publisher: Nature Research
ISSN: 2041-1723
Date of First Compliant Deposit: 30 March 2016
Date of Acceptance: 2 December 2013
Last Modified: 05 May 2023 23:32
URI: https://orca.cardiff.ac.uk/id/eprint/79450

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