Kidney Week

Abstract: FR-PO0955

Bridging Innate and Adaptive Immunity as a Potential Mechanism for Tubulointerstitial Injury in Pediatric Patients with Nephrotic Syndrome

Session Information

• Pediatric Nephrology: Genetic Diseases, Development, Neonatal Nephrology, Glomerular Diseases, and More
  October 23, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

• 1800 Pediatric Nephrology

Authors

• Dalal, Vidhi, Ann and Robert H. Lurie Children's Hospital of Chicago Pediatric Nephrology, Chicago, Illinois, United States

Vidhi Dalal, MD

• Olson, Eli C., Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States

Eli C. Olson, PhD

• Zhou, Yalu, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States

Yalu Zhou, MS, MSc

• Deb, Dilip K., Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States

Dilip K. Deb, PhD

• Eisenbarth, Stephanie, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States

Stephanie Eisenbarth, MD

• Quaggin, Susan E., Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States

Susan E. Quaggin, MD, FASN

Background

Nephrotic syndrome (NS) is a major cause of childhood end stage kidney disease (ESKD). The massive proteinuria and glomerular dysfunction that define this condition ultimately damage the renal tubulointerstitium, causing progressive interstitial fibrosis and tubular atrophy (IFTA), the histologic signatures of ESKD. Inflammation has been implicated as a contributor to the tubulointerstitial pathology of NS, but the specific mechanisms underlying this immune-mediated injury are not well-understood. We have found an expansion of conventional type 1 dendritic cells (cDC1s) in the kidneys of young mice with congenital NS and aim to determine if these cells drive inflammation and renal fibrosis in NS via activation of CD8+ cytotoxic T-cells (CTLs).

Methods

Mice with congenital NS were generated by deleting transcription factor 21 (Tcf21) from podocyte precursors (Tcf21-KO mice). Single cell RNA sequencing (scRNAseq) was performed on kidneys from Tcf21-KO mice and littermate controls between 2-3 weeks of age to identify immune changes in the tubulointerstitium of young proteinuric mice. Findings from scRNAseq were validated by immunostaining and flow cytometry.

Results

Single cell RNA sequencing (scRNAseq) showed an expansion of mature, activated cDC1s in Tcf21-KO kidneys. This finding was confirmed by flow cytometry and immunostaining. Consistent with the ability of cDC1s to activate CTLs, our scRNAseq data also showed an expansion of proliferating and effector CTLs in Tcf21-KO kidneys. Tcf21-KO mice are now being crossed to Irf8 +32^-/- (Delta32, D32) mice that lack cDC1s. Using a combination of functional, histologic, and molecular analyses, we will determine if the absence of cDC1s protects the kidneys of Tcf21-KO mice from CTL-mediated inflammation and tubulointerstitial fibrosis.

Conclusion

Mice with congenital NS demonstrate a dramatic increase in the number of cDC1s with a corresponding increase CTL activation. The upregulation of activation markers and effector molecules (such as granzymes) by the CTLs in Tcf21-KO kidneys suggests that cDC1s activate CTLs to damage the renal tubulointerstitium in these mice. Tcf21-KO mice lacking cDC1s are being used to verify this hypothesis and establish a potential mechanism by which innate and adaptive immunity are bridged to cause tubulointerstitial injury in childhood NS.

Funding

• NIDDK Support