Abstract: SA-PO0212
Altered Bone Marrow Granulopoiesis in Kidney Diseases: SGLT2 in Immune Cells Beyond the Kidneys
Session Information
- CKD: Mechanisms of Injury and Fibrosis - 3
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2203 CKD (Non-Dialysis): Mechanisms
Authors
- Jimenez Uribe, Alexis P., Rush University Medical Center, Chicago, Illinois, United States
- Cao, Yanxia, Rush University Medical Center, Chicago, Illinois, United States
- Spear, Ryan, Rush University Medical Center, Chicago, Illinois, United States
- Mangos, Steve, Rush University Medical Center, Chicago, Illinois, United States
- Vincenti, Flavio, University of California San Francisco School of Medicine, San Francisco, California, United States
- Reiser, Jochen, The University of Texas Medical Branch at Galveston, Galveston, Texas, United States
- Hahm, Eunsil, Rush University Medical Center, Chicago, Illinois, United States
Background
Our recent study demonstrated that inflammatory bone marrow (BM) remodeling drives monocyte reprogramming and contributes to kidney injury. However, how inflammatory BM conditions affect granulocyte differentiation and function remains unclear. Although SGLT2 inhibitors exert anti-inflammatory effects beyond glucose lowering, SGLT2 expression and function in immune cells remain poorly understood. Here, we investigated whether SGLT2 is expressed during inflammatory granulopoiesis and regulates immature granulocyte function.
Methods
Human CD34+ hematopoietic stem cells and HL-60 myeloblast cells were differentiated toward granulocytes under basal or inflammatory conditions. Metabolic markers, inflammatory markers, and SGLT2 expression were assessed by multicolor flow cytometry. SGLT2+ immune populations were analyzed in mouse peripheral blood, spleen, and BM after LPS-induced systemic inflammation. Single-cell RNA sequencing of BM mononuclear cells from CKD patients and healthy donors was examined. Empagliflozin was used to test the effect of SGLT2 inhibition on granulocyte oxidative burst.
Results
Inflammatory conditions induced metabolic alteration during granulocytic differentiation, characterized by increased mitochondrial mass, catabolic metabolism, and IL-8 production. SGLT2 and NAD-linked enzyme CD38 was enriched in early immature granulocytic populations and declined with maturation, whereas LPS or TNFα preserved SGLT2 expression during HL-60 differentiation. In mice, SGLT2+ immune cells were primarily detected in BM, but were rare in peripheral blood or spleen, and significantly expanded following LPS-induced inflammation. Single-cell RNA sequencing of BM cells from CKD patients identified metabolically activated immature granulocytes with hyperinflammatory emergency granulocyte-like signatures compared to healthy donors. Empagliflozin reduced ROS production during HL-60 differentiation, supporting a direct role for SGLT2 in inflammatory granulopoiesis.
Conclusion
Our findings identify a previously unrecognized SGLT2+ immature granulocytic population in BM with metabolically activated and hyperinflammatory features. These data suggest a novel role for SGLT2 in early myeloid cell function during chronic inflammation and may provide insight into the anti-inflammatory effects of SGLT2 inhibitors.
Acknowledgment
This work is supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institute of Health under Award Number R01DK132072.
Funding
- NIDDK Support