Abstract: FR-PO287
Acute Inflammation Enhances SGLT2-Positive Myeloid Population in Bone Marrow
Session Information
- Diabetic Kidney Disease: Basic - 1
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 701 Diabetic Kidney Disease: Basic
Authors
- Alcantar, Ariana G., Rush University Medical Center, Chicago, Illinois, United States
- 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
- Reiser, Jochen, The University of Texas Medical Branch at Galveston Development Office, Galveston, Texas, United States
- Hahm, Eunsil, Rush University Medical Center, Chicago, Illinois, United States
Group or Team Name
- Hahm Lab.
Background
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have exhibited benefits beyond controlling blood sugar levels, including improving cardiac function. Since SGLT2 expression predominantly occurs in kidney proximal tubule cells, understanding SGLT2 expression and its pathophysiological functions outside the kidney remains limited. This study aims to investigate the expression of SGLT2 in immune cells and its implications.
Methods
Leukocytes were isolated from peripheral blood and bone marrow (BM) of BALB/c and C57BL/6 mice under normal conditions and after lipopolysaccharide (LPS)-induced systemic inflammation. CD34+ human hematopoietic cells (HSCs) from healthy donors and the human myelocyte cell line (HL-60) were cultured to study for in vitro myelopoiesis. Staining for SGLT2 and cell markers was performed using multicolor flow cytometry.
Results
Under normal conditions, approximately 1.5% of mouse BM contains an SGLT2+ population that expresses myeloid markers (Ly6C and Ly6G) but not lymphoid markers (CD3 and CD19). Interestingly, this SGLT2+ population increases after LPS challenge in bone marrow, not in peripheral blood. Further characterization shows that these cells display an immature phenotype (Sca-1+), arise from the myeloid lineage (CD11b+), and are monocytic in nature (CD14+). Consistent with our in vivo results, in vitro myelopoiesis assays demonstrated that inflammatory signals (TNFa or LPS) increase the SGLT2+ myeloid cells during cell differentiation.
Conclusion
This study reveals that SGLT2 expression is not limited to the kidney. In both mouse and human immune systems, we identified a myeloid population of SGLT2+ cells in the bone marrow that increases under inflammatory conditions. While further investigation is necessary to understand the role of SGLT2 in BM myeloid cells during inflammation, our results imply a novel role for SGLT2 in immune cells. This points to potential clinical implications of SGLT2 inhibitors on immune regulation.
Funding
- NIDDK Support