GEO series
High-Fat Diet Causes Rapid Loss of Intestinal Group 3 Innate Lymphoid Cells Through Microbiota-Driven Inflammation
GSE317764
Homo sapiens; Mus musculus
Expression profiling by high throughput sequencing
270 samples
Submitted 2026/05/26
Platform GPL19057Platform GPL18573
Summary
Group 3 innate lymphoid cells (ILC3s) are critical sensory hubs to maintain intestinal immunity while adapting to environmental changes, including food intake and microbiota composition. Nutritional stress such as feeding on a high-fat diet (HFD) impairs ILC3s homeostasis, but the drivers underlying this phenotype remain elusive. Here, we found that intestinal ILC3s are depleted in overweight and obese humans, similarly to HFD-induced obese mice. However, we identified that ILC3s loss is not dependent on excessive calorie intake, weight gain, or glucose intolerance. Instead, we found that ILC3s impairment starts upon hours of HFD consumption, inducing microbial efflux. As a result, tissue-resident mononuclear phagocytes (MNPs) become proinflammatory, driving ILC3 cell death. We determined that the microbiota-driven stimulation overrides lipid-laden ILC3s ability to perform fatty acid oxidation, causing mitochondrial damage due to the accumulation of lipid peroxides. Collectively, our findings define the mechanism driving ILC3s maladaptation to fat-microbiota crosstalk and raise new considerations for understanding intestinal homeostasis and inflammation.
Published in
Torrico EC, Kaptein P, Laalouhmi F et al.
· Immunity 2026
· PMID 41916320
· doi:10.1016/j.immuni.2026.02.014
This dataset
Download
Direct links to NCBI, no account and no request form: the whole study as GSE317764_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 270 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1415199 and SRA study SRP667836. Searching any of these in the dataset finder brings you back here.
Study design
17 conditions, mostly in duplicate
TH17 , Obese, Sample ×4
MNP , Obese, Sample ×3
Duodenum, DIO, 12Wks, Sample ×3
ILC3 , Obese, sample3, ×2
ILC3, Obese, Sample ×2
MNP , Obese, Sample 6, ×2
ILC3 , Obese, Sample 6, ×2
ILC3 , Lean, Sample 2, ×2
+11 more
Supports a between-group comparison across 38 samples.
17 replicated groups read from the first 40 of 270 sample titles; they account for 38 of them. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM9477825 ILC3 , Obese, sample3, rep 1
- GSM9477826 ILC3 , Obese, sample3, rep 2
- GSM9477827 ILC3 , Obese, Sample 1
- GSM9477828 MNP , Obese, Sample 1
- GSM9477829 TH17 , Obese, Sample 1
- GSM9477830 ILC3, Obese, Sample 2
- GSM9477831 MNP , Obese, Sample 2
- GSM9477832 TH17 , Obese, Sample 2
- GSM9477833 MNP , Obese, Sample 6, rep 1
- GSM9477834 MNP , Obese, Sample 6, rep 2
- GSM9477835 TH17 , Obese, Sample 3
- GSM9477836 TH17 , Obese, Sample 4
- GSM9477837 ILC3 , Obese, Sample 6, rep 1
- GSM9477838 ILC3 , Obese, Sample 6, rep 2
- GSM9477839 ILC3 , Lean, Sample 2, rep 1
- GSM9477840 ILC3 , Lean, Sample 2, rep 2
- GSM9477841 ILC3 , Lean, Sample 1, rep 1
- GSM9477842 ILC3 , Lean, Sample 1, rep 2
- GSM9477843 TH17 , Lean, Sample1
- GSM9477844 MNP , Lean, Sample 2
- GSM9477845 ILC3 , Obese, Sample 4, rep 1
- GSM9477846 ILC3, Obese, Sample 5
- GSM9477847 ILC3 , Obese, Sample 4, rep 2
- GSM9477848 MNP , Lean, Sample 2, rep 1
- GSM9477849 MNP , Lean, Sample 2, rep 2
- GSM9477850 TH17, Lean, Sample 3, rep 1
- GSM9477851 TH17, Lean, Sample 3, rep 2
- GSM9477852 ILC3 , Obese, Sample 7, rep 1
- GSM9477853 ILC3 , Obese, Sample 7, rep 2
- GSM9477854 MNP , Obese, Sample 4
- GSM9477855 MNP , Lean, Sample 3
- GSM9477856 TH17 , Lean, Sample 3
- GSM9477857 MNP , Obese, Sample 5, rep 1
- GSM9477858 MNP , Obese, Sample 5, rep 2
- GSM9477859 ILC3 , Lean Sample 3, rep 1
- GSM9477860 ILC3 , Lean Sample 3, rep 2
- GSM9477861 Duodenum, DIO, 12Wks, Sample 1
- GSM9477862 Duodenum, DIO, 12Wks, Sample 2
- GSM9477863 Duodenum, DIO, 12Wks, Sample 3
- GSM9477864 Duodenum, Chow diet, 12Wks, Sample 1
+ 230 more — browse all 270 samples with per-sample file links →
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