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During the congress, E-Posters will be accessible to all participants on the congress website 24/7, as well as in the E-poster stations in the congress center.
Preparing your E-Poster
Please review the E-Poster format requirements carefully when preparing your E-Poster. Should your E-Poster not meet the mentioned requirements, it may not be displayed as described above.
E-Poster Submission Deadline
Please prepare and upload your E-Poster no later than March 14, 2026 11.59PM CET. After this date, you will no longer be able to prepare and upload your E-poster and it will not be displayed and accessible on the congress website.
Please follow the instructions below to input your abstract title.
Abstract titles should be brief and reflect the content of the abstract.
Chronic Kidney Disease (CKD) significantly increases the risk of inflammatory bowel disease (IBD), suggesting a critical disruption of the gut-kidney axis. Intestinal group 3 innate lymphoid cells (ILC3s) are crucial guardians of gut homeostasis via IL-22 secretion, but their functional fate during CKD remains unknown. We hypothesized that functional impairment of intestinal ILC3s mediates the CKD-driven colitis susceptibility.
CKD was established using Unilateral Ureteral Obstruction (UUO) and Folic Acid Nephropathy (FAN) models, followed by Dextran Sodium Sulfate (DSS) challenge to induce colitis. The role of ILC3s was characterized using genetic deletion and adoptive transfer models. Single-cell RNA sequencing (scRNA-seq) of intestinal ILC3s sorted from sham or UUO mice was performed to identify molecular regulatory mechanisms. Pharmacological inhibitors and exogenous mediators, including indoxyl sulfate (IS), recombinant IL-22 and CD36 inhibitor SSO, were employed for mechanistic validation.
Both UUO-DSS and FAN-DSS mice exhibited exacerbated colitis phenotypes, characterized by accelerated weight loss, shortened colon, and extensive epithelial damage. The susceptibility of colitis was also observed in ILC3-sufficient RorcGFP/+-UUO mice, whereas the difference was diminished in ILC3-depletion RorcGFP/GFP-UUO mice, demonstrating that ILC3s are required to mediate colitis susceptibility. Crucially, transfer of dysfunctional UUO-derived ILC3s was sufficient to transmit the colitis susceptibility phenotype to recipients. ScRNA-seq identified suppressed Transglutaminase 2 (TGM2) expression in UUO-ILC3s, causally linked to lower IL-22 production. The circulating uremic toxin IS was identified as the upstream driver, as CKD patients’ plasma and IS treatment downregulated TGM2 and IL-22 expression in ILC3s. Subsequently, this persistent IL-22 deficiency triggered a metabolic feedback loop by upregulating intestinal epithelial lipid transporter CD36. This enhanced lipid absorption and accumulation, which in turn induced ILC3 lipotoxicity and further suppressed IL-22 production. Targeting CD36 with SSO reduced lipid accumulation and restored ILC3 IL-22 production, mitigating UUO-driven colitis susceptibility.
We define a sequential and self-perpetuating mechanism where deficiency and loss-of-function of ILC3s are central to renal injury-driven colitis susceptibility. Early systemic accumulation of IS acutely suppresses the intrinsic TGM2-IL-22 axis in ILC3s. Subsequently, chronic IL-22 deficiency upregulates intestinal epithelial CD36 and establishes a pathogenic local metabolic environment that further inhibits IL-22 secretion of ILC3s. These findings propose that IS clearance and CD36 inhibition represent dual therapeutic strategies to restore ILC3 function and intestinal homeostasis in CKD.
