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| Status |
Public on Jun 20, 2024 |
| Title |
Uremic toxin indoxyl sulfate induces trained immunity via the AhR-dependent arachidonic acid pathway in end-stage renal disease [RNAseq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Trained immunity is the long-term functional reprogramming of innate immune cells, which results in altered responses toward a secondary challenge. Despite indoxyl sulfate (IS) being a potent stimulus associated with chronic kidney disease (CKD)-related inflammation, its impact on trained immunity has not been explored. Here, we demonstrate that IS induces trained immunity in monocytes via epigenetic and metabolic reprogramming, resulting in augmented cytokine production. Mechanistically, the aryl hydrocarbon receptor (AhR) contributes to IS-trained immunity by enhancing the expression of arachidonic acid (AA) metabolism-related genes such as Arachidonate 5-Lipoxygenase (ALOX5) and ALOX5 Activating Protein (ALOX5AP). Inhibition of AhR during IS training suppresses the induction of IS-trained immunity. Monocytes from end-stage renal disease (ESRD) patients have increased ALOX5 expression and after 6-day training, they exhibit enhanced TNF-α and IL-6 production to LPS. Furthermore, healthy control-derived monocytes trained with uremic sera from ESRD patients exhibit increased production of TNF-α and IL-6. Consistently, IS-trained mice and their splenic myeloid cells had increased production of TNF-α after in vivo and ex vivo LPS stimulation compared to that of control mice. These results provide insight into the role of IS in the induction of trained immunity, which is critical during inflammatory immune responses in CKD patients.
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| Overall design |
To investigate the mechanism involved in IS-induced trained immunity, we performed RNA-seq using IS-trained cells and non-trained cells at 6 days. Differentially expressed genes (DEGs) and gene oncology (GO) pathways were analyzed
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| Contributor(s) |
Kim H, Lee S, Lee W |
| Citation(s) |
38980302 |
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| Submission date |
Apr 02, 2024 |
| Last update date |
Aug 02, 2024 |
| Contact name |
Hee Young Kim |
| E-mail(s) |
hyk0801@hotmail.com
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| Organization name |
Seoul National University College of Medicine
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| Department |
Department of Microbiology and Immunology
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| Street address |
103 Daehak-ro, Jongno-gu,
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| City |
Seoul |
| ZIP/Postal code |
03080 |
| Country |
South Korea |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (9)
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| GSM8183535 |
IS-induced trained immunity-1, 6 days |
| GSM8183536 |
IS-induced trained immunity-2, 6 days |
| GSM8183537 |
IS-induced trained immunity-3, 6 days |
| GSM8183538 |
GNF351-preteated IS-trained immunity-1, 6 days |
| GSM8183539 |
GNF351-preteated IS-trained immunity-2, 6 days |
| GSM8183540 |
GNF351-preteated IS-trained immunity-3, 6 days |
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| Relations |
| BioProject |
PRJNA1095463 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE263024_Expression_Profile.GRCh37.transcript-1.xlsx |
12.7 Mb |
(ftp)(http) |
XLSX |
| GSE263024_Expression_Profile.GRCh37.transcript-2.xlsx |
9.2 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
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