Abstract: TH-OR008
Trafficking of Intestinal Peyer Patches Immune Cells to Kidneys: Novel Mechanism by Which Gut Microbiome Modulates AKI
Session Information
- AKI Progression and Resolution: Cellular and Molecular Insights
November 06, 2025 | Location: Room 320A, Convention Center
Abstract Time: 05:40 PM - 05:50 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Patel, Shishir Kumar, Johns Hopkins Medicine, Baltimore, Maryland, United States
- Yao, Jiahui, Johns Hopkins Medicine, Baltimore, Maryland, United States
- Kapoor, Radhika, Johns Hopkins Medicine, Baltimore, Maryland, United States
- Fallah Rastegar, Tara, Johns Hopkins Medicine, Baltimore, Maryland, United States
- Matsuura, Ryo, Johns Hopkins Medicine, Baltimore, Maryland, United States
- Cahan, Patrick, Johns Hopkins Medicine, Baltimore, Maryland, United States
- Noel, Sanjeev, Johns Hopkins Medicine, Baltimore, Maryland, United States
- Rabb, Hamid, Johns Hopkins Medicine, Baltimore, Maryland, United States
Background
The gut microbiome has been shown to modify outcomes from experimental AKI. However, the precise mechanisms are not known. One possible mechanism is by modulating immune cell trafficking and function into AKI kidney. We hypothesized that the intestinal Peyer’s patches were a potential source of kidney immune cells infiltration during AKI.
Methods
Male B6 mice treated with AMX or vehicle for 15 days, and germ-free (GF) mice, underwent 50-minute unilateral ischemia-reperfusion injury (UIR). Peyer’s patches (PP) were labeled with CellTrace Far Red or CFSE dye, immediately or 48h post-surgery, followed by in vivo imaging. Kidney and small intestine were harvested at 72h or 7 days post-UIR for immunophenotyping. scRNAseq analysis on CD3+ sorted cells from gut and kidney were performed to identify potential chemokines involved in immune cell trafficking. After identification of chemokine CXCR6, mice received 100 µg anti-CXCR6 antibody or isotype every other day post-UIR, till day 7 followed by evaluation of kidney tissue and GFR measurements.
Results
In vivo whole mouse imaging demonstrated that PP labeled cells migrated to the injured kidney. Flow data showed also migration of immune cells from PP to the kidney following AKI. At three days post-UIR, the percentage of CD3+ CFSE+ cells significantly increased in the kidneys of normal mice (Control: 37.4 ± 5.2, UIR: 76.8 ± 3.6, p<0.0001); however, it decreased in germ-free mice UIR compared to UIR in standard conditions (Control: 21.35±0.9, GF-control: 28.07 ± 1.8, UIR: 69.18 ± 10.31, GF-UIR: 40.5 ± 8.2, p < 0.0001). Similar observations were made in the 7-day groups. Blocking CXCR6 reduced CD3 cell migration (IgG:26.70±3.1, CXCR6:19.30±1.0, <0.0001) and renal fibrosis (IgG:21.20±3.8, CXCR6:16.60±3.7), but did not change GFR. scRNAseq data revealed CXCR6 and pdcd1 co-expression on effector memory cells and in the kidneys.
Conclusion
Immune cells migrate from intestinal Peyer’s patches to the injured kidney after severe UIR, and the absence of gut microbiota reduced this migration. Blocking CXCR6 decreased PP migration of cells to kidney and reduced kidney fibrosis. This data identifies novel mechanisms by which the gut microbiome modulates outcomes from AKI.
Funding
- NIDDK Support