Data from: LRP5-dependent transport of polyunsaturated fatty acids serves as an immune checkpoint for natural killer cells
Data files
Jul 24, 2026 version files 38.85 KB
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Phospholipid_abundance_in_WT_and_Lrp5-KO_NK_cells.xlsx
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README.md
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Abstract
Polyunsaturated fatty acids (PUFAs) play a crucial role in tumor development by influencing not only tumor cells but also immune cells within the tumor microenvironment. Elucidating the mechanism and function of PUFA transport within immune cells is important for understanding tumor regulation. In this study, we found that LDL Receptor-Related Protein 5 (LRP5) plays an essential role in modulating natural killer (NK) cell antitumor function by facilitating polyunsaturated fatty acid (PUFA) transport through its LDLa domain. The loss of LRP5, and particularly of its LDLa domain, in NK cells enhanced their cytotoxicity and antitumor activity both in vivo and in vitro. However, under PUFA-depleted dietary or culture conditions, wild-type NK cells also exhibited enhanced cytotoxicity, eliminating the functional difference between wild-type and LDLa domain–deficient NK cells. Mechanistically, LRP5-mediated PUFA transport suppressed mTORC1 signaling and glycolysis in NK cells, a pathway essential for NK cell cytotoxicity. Thus, our study identifies LRP5 as a critical immune checkpoint that restrains NK cell activity through PUFA transport–dependent suppression of mTORC1 signaling.
Dataset DOI: 10.5061/dryad.qfttdz0z1
Description of the data and file structure
File: Phospholipid_abundance_in_WT_and_Lrp5-KO_NK_cells.xlsx
Triplicate NK cell samples were prepared from the Lrp5cko and WT control mice. Each sample consists of 3 million NK cells pooled from three mice. The cells were washed in PBS containing 1% fatty acid-free BSA for three times and snap-frozen in liquid nitrogen before being stored at -80°C. The frozen samples were shipped on dry ice to Lipotype GmbH (Dresden, Germany), where they were extracted and analyzed using the Shotgun Lipidomic Platform. Intensity of lipid class-specific internal standards was used for lipid quantification. For data quality control, The dynamic range for cell culture samples was determined prior to analysis. Based on these data, limits of quantification and coefficients of variation for the different lipid classes were determined. Each analysis is accompanied by a set of blank samples to control for a background and a set of quality control reference samples to control for intra-run reproducibility and sample specific issues.
In terms of Lipid nomenclature, for example PI 18:1_ 16:0 denotes phosphatidylinositol with octadecenoic (18:1) and hexadecanoic (16:0) fatty acids, for which the exact position (sn-1 or sn-2) in relation to the glycerol backbone cannot be discriminated (underline “_” separating the acyl chains). On contrary, PC O-18:1/ 16:0 denotes an ether- phosphatidylcholine, where an alkyl chain with 18 carbon atoms and 1 double bond (O-18:1) is ether-bound to sn-1 position of the glycerol and a hexadecanoic acid (16:0) is connect via an ester bond to the sn-2 position of the glycerol (slash “/” separating the chains signifies that the sn-position on the glycerol can be resolved).
Columns:
feature: lipid nomenclature described above
WT-NKcell-1 to KO-NKcell-3: lipid quantification analyzed using the Shotgun Lipidomic Platform, reported for control (WT) and knockout (KO) mouse cell samples as described above