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Abstract: FR-PO830

Single-Cell RNA Sequencing Uncovers Distinct Clusters of T Helper 17 Cells In Renal Autoimmune Disease

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Kilian, Christoph, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Borchers, Alina, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Bartsch, Patricia, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Zhao, Yu, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Panzer, Ulf, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Krebs, Christian F., University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Background

T cells play a pivotal role in the pathogenesis in various autoimmune diseases by their ability to differentiate into pathogenic effector Th1 and Th17 cells, this includes human and experimental glomerulonephritis. CD4+ T cells and Th17 cells in particular can have a high degree of plasticity in the brain and intestine but show limited spontaneous plasticity in the kidney. However, the mechanisms that control stability and transdifferentiation of Th17 cells into alternate subsets and the impact of T cell plasticity on autoimmunity are incompletely understood.

Methods

To address the heterogeneity and plasticity of renal Th17 cells in experimental glomerulonephritis in more detail in an unbiased approach, we established single cell RNA-sequencing of FACS-sorted T cells from the kidney in experimental crescentic glomerulonephritis (cGN, NTN).

Results

Here, we report data from 6,841 eYFP positive renal Th17 cells from IL-17A fate reporter mice (Il17aCre x R26reYFP). Our analysis unveiled a pronounced variety within this population. We discovered 10 clusters based on transcriptional similarities. Overall, in 25% of all cells we could detect IL-17A mRNA. These actively IL-17A-expressing cells are enriched in 3 clusters, which underscores the heterogeneity of our dataset. Interestingly, 25% of IL-17A negative cells (exTh17) display expression profiles of inactive states. Moreover, one cluster of cells with a Th1 profile emerged from Th17 cells and one cluster displays high Foxp3 expression indicating transdifferentiation of Th17 cells into Th1 cells and regulatory T cells, respectively.

Conclusion

In summary, our single cell atlas of renal Th17 cells shows a high degree of heterogeneity and expression profiles of the different clusters could build the basis for the analysis of potential cell-cell crosstalk that include resident kidney cells.