TY - JOUR
T1 - A lipid atlas of human and mouse immune cells provides insights into ferroptosis susceptibility
AU - Morgan, Pooranee K.
AU - Pernes, Gerard
AU - Huynh, Kevin
AU - Giles, Corey
AU - Paul, Sudip
AU - Smith, Adam Alexander T.
AU - Mellett, Natalie A.
AU - Liang, Amy
AU - van Buuren-Milne, Tilly
AU - Veiga, Camilla Bertuzzo
AU - Collins, Thomas J.C.
AU - Xu, Yangsong
AU - Lee, Man K.S.
AU - De Silva, T. Michael
AU - Meikle, Peter J.
AU - Lancaster, Graeme I.
AU - Murphy, Andrew J.
N1 - Funding Information:
We thank the members of the ARA Flow Cytometry Core Facility for expert assistance. We thank the members of ARA Animal Services who provided wonderful care of the mice used in this work. We thank all of the human volunteers who provided blood samples to assist with this work. We acknowledge staff at the facilities where the Acsl4 mice were generated, including those at the MAGEC laboratory who provided scientific and technical assistance. MAGEC is supported by Phenomics Australia. Phenomics Australia is supported by the Australian Government through the National Collaborative Research Infrastructure Strategy programme. We are grateful to C. Sobey for providing access to the Nox2 mice. Schematic figures were created using Biorender.com . We are extremely grateful to the following funding sources: National Health and Medical Research Council of Australia (grants GNT1189012 (to G.I.L.), GNT1194329 (to A.J.M.), GNT1197190 (to K.H.) and GNT2009965 (to P.J.M.)), a CSL Centenary Fellowship (to A.J.M.) and the Victorian Government\u2019s Operational Support Program. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
Publisher Copyright:
© The Author(s), under exclusive licence to Springer Nature Limited 2024.
PY - 2024/4
Y1 - 2024/4
N2 - The cellular lipidome comprises thousands of unique lipid species. Here, using mass spectrometry-based targeted lipidomics, we characterize the lipid landscape of human and mouse immune cells (www.cellularlipidatlas.com). Using this resource, we show that immune cells have unique lipidomic signatures and that processes such as activation, maturation and development impact immune cell lipid composition. To demonstrate the potential of this resource to provide insights into immune cell biology, we determine how a cell-specific lipid trait—differences in the abundance of polyunsaturated fatty acid-containing glycerophospholipids (PUFA-PLs)—influences immune cell biology. First, we show that differences in PUFA-PL content underpin the differential susceptibility of immune cells to ferroptosis. Second, we show that low PUFA-PL content promotes resistance to ferroptosis in activated neutrophils. In summary, we show that the lipid landscape is a defining feature of immune cell identity and that cell-specific lipid phenotypes underpin aspects of immune cell physiology.
AB - The cellular lipidome comprises thousands of unique lipid species. Here, using mass spectrometry-based targeted lipidomics, we characterize the lipid landscape of human and mouse immune cells (www.cellularlipidatlas.com). Using this resource, we show that immune cells have unique lipidomic signatures and that processes such as activation, maturation and development impact immune cell lipid composition. To demonstrate the potential of this resource to provide insights into immune cell biology, we determine how a cell-specific lipid trait—differences in the abundance of polyunsaturated fatty acid-containing glycerophospholipids (PUFA-PLs)—influences immune cell biology. First, we show that differences in PUFA-PL content underpin the differential susceptibility of immune cells to ferroptosis. Second, we show that low PUFA-PL content promotes resistance to ferroptosis in activated neutrophils. In summary, we show that the lipid landscape is a defining feature of immune cell identity and that cell-specific lipid phenotypes underpin aspects of immune cell physiology.
UR - https://www.scopus.com/pages/publications/85189617962
U2 - 10.1038/s41556-024-01377-z
DO - 10.1038/s41556-024-01377-z
M3 - Article
C2 - 38589531
AN - SCOPUS:85189617962
SN - 1465-7392
VL - 26
SP - 645
EP - 659
JO - Nature Cell Biology
JF - Nature Cell Biology
IS - 4
ER -