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

First Author  Brailey PM Year  2022
Journal  Nat Commun Volume  13
Issue  1 Pages  6723
PubMed ID  36344546 Mgi Jnum  J:337613
Mgi Id  MGI:7386205 Doi  10.1038/s41467-022-34532-x
Citation  Brailey PM, et al. (2022) CD1d-dependent rewiring of lipid metabolism in macrophages regulates innate immune responses. Nat Commun 13(1):6723
abstractText  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.
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