Kidney Week

Abstract: TH-PO0656

Identification of Th17 Cells with Stemness Features in Crescentic Glomerulonephritis

Session Information

• Glomerular Diseases: Immunopathogenesis and Targeted Therapeutics
  November 06, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

• Lin, Mingjie, Universitatsklinikum Hamburg-Eppendorf, Hamburg, HH, Germany

Mingjie Lin

• Shaikh, Nikhat, Universitatsklinikum Hamburg-Eppendorf, Hamburg, HH, Germany

Nikhat Shaikh, PhD

• Hellmig, Malte, Universitatsklinikum Hamburg-Eppendorf, Hamburg, HH, Germany

Malte Hellmig

• Hube, Arthur L., Universitatsklinikum Hamburg-Eppendorf, Hamburg, HH, Germany

Arthur L. Hube

• Piegsa, Vincent, Universitatsklinikum Hamburg-Eppendorf, Hamburg, HH, Germany

Vincent Piegsa

• Sivayoganathan, Varshi, Universitatsklinikum Hamburg-Eppendorf, Hamburg, HH, Germany

Varshi Sivayoganathan, PhD

• Borchers, Alina, Universitatsklinikum Hamburg-Eppendorf, Hamburg, HH, Germany

Alina Borchers

• Kittmann, Enrico, Universitatsklinikum Hamburg-Eppendorf, Hamburg, HH, Germany

Enrico Kittmann

• Jauch-Speer, Saskia-L., Universitatsklinikum Hamburg-Eppendorf, Hamburg, HH, Germany

Saskia-L. Jauch-Speer, PhD

• Sultana, Zeba, Universitatsklinikum Hamburg-Eppendorf, Hamburg, HH, Germany

Zeba Sultana, MS, MSc

• Huber, Tobias B., Universitatsklinikum Hamburg-Eppendorf, Hamburg, HH, Germany

Tobias B. Huber, MD, FASN

• Mittrücker, Hans-willi, Universitatsklinikum Hamburg-Eppendorf, Hamburg, HH, Germany

Hans-willi Mittrücker, PhD

• Panzer, Ulf, Universitatsklinikum Hamburg-Eppendorf, Hamburg, HH, Germany

Ulf Panzer, MD

• Krebs, Christian F., Universitatsklinikum Hamburg-Eppendorf, Hamburg, HH, Germany

Christian F. Krebs, MD

Background

Th17 cells are key drivers of autoimmune diseases, but how they persist in renal autoimmunity remains unclear. The role of stem-like Th17 cells in this context has not been explored so far. Here, we explore Th17 cell heterogeneity, function and differentiation in ANCA-associated glomerulonephritis (ANCA-GN) and in experimental GN.

Methods

We performed scRNA-seq and flow cytometry on kidney and blood samples from ANCA-GN patients, experimental crescentic GN (nephrotoxic nephritis, NTN) model and mouse Staphylococcus aureus (S. aureus) infection to profile Th17 subsets. Adoptive transfer of SLAMF6⁺ and SLAMF6^- Th17 cells from NTN mice into Rag1^-/- recipients assessed self-renewal and pathogenicity. Single-cell trajectory analyses and adoptive transfers in the infection model evaluated Th17 differentiation. IL-17A^Cre × Tcf7^fl/fl conditional knockout mice tested transcriptional regulation. IL-7 stimulation of patient Th17 cells was performed in vitro.

Results

From the kidney of ANCA-GN patients, we identified stem-like Th17 with high TCF7 expression and tissue-resident memory Trm17 cells. Transferred stem-like SLAMF6⁺ Th17 cells from NTN mice maintained self-renewal capacity in Rag1^-/- recipients. Single-cell trajectory analysis in both human ANCA-GN and mouse models revealed a differentiation pathway from stem-like Th17 to Trm17 cells. Notably, SLAMF6⁺ Th17 cells gave rise to CXCR6⁺CD69⁺ Trm17 cells in Rag1^-/- recipients with S. aureus infection. Conditional deletion of TCF7 in IL17A^Cre Tcf7^fl/fl mice reduced both Th17 subsets, impaired cytokine production, and suppressed proliferation, indicating a functional role of TCF7 in Th17 cell maintenance.

Conclusion

Stem-like Th17 cells show TCF7-dependent self-renewal and differentiation into Trm17 cells and thereby might contribute to autoimmune kidney. The IL-7/CXCR6 axis may promote tissue retention, identifying potential therapeutic targets in renal autoimmunity.

Funding

• Government Support – Non-U.S.

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025zzm8dxka