CD1d-dependent rewiring of lipid metabolism in macrophages regulates innate immune responses

Brailey, Phillip M., Evans, Lauren, López-Rodríguez, Juan Carlos, Sinadinos, Anthony, Tyrrel, Victoria, Kelly, Gavin, O’Donnell, Valerie, Ghazal, Peter ORCID: https://orcid.org/0000-0003-0035-2228, John, Susan and Barral, Patricia 2022. CD1d-dependent rewiring of lipid metabolism in macrophages regulates innate immune responses. Nature Communications 13 , 6723. 10.1038/s41467-022-34532-x

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Abstract

Alterations in cellular metabolism underpin macrophage activation, yet little is known regarding how key immunological molecules regulate metabolic programs in macrophages. Here we uncover a function for the antigen presenting molecule CD1d in the control of lipid metabolism. We show that CD1d-deficient macrophages exhibit a metabolic reprogramming, with a downregulation of lipid metabolic pathways and an increase in exogenous lipid import. This metabolic rewiring primes macrophages for enhanced responses to innate signals, as CD1d-KO cells show higher signalling and cytokine secretion upon Toll-like receptor stimulation. Mechanistically, CD1d modulates lipid import by controlling the internalization of the lipid transporter CD36, while blocking lipid uptake through CD36 restores metabolic and immune responses in macrophages. Thus, our data reveal CD1d as a key regulator of an inflammatory-metabolic circuit in macrophages, independent of its function in the control of T cell responses.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Additional Information:	License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by/4.0/, Type: open-access
Publisher:	Nature Research
Date of First Compliant Deposit:	9 November 2022
Date of Acceptance:	27 October 2022
Last Modified:	11 Oct 2023 21:42
URI:	https://orca.cardiff.ac.uk/id/eprint/154064

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