Kidney Week

Abstract: SA-OR022

Staphylococcus Aureus-Induced Tissue Resident Memory T Helper 17 Cells (T_RM17 Cells) Drive Renal Autoimmune Disease

Session Information

• ANCA It Is
  November 09, 2019 | Location: 207, Walter E. Washington Convention Center
  Abstract Time: 04:42 PM - 04:54 PM

Category: Glomerular Diseases

• 1202 Glomerular Diseases: Immunology and Inflammation

Authors

• Krebs, Christian F., University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Christian F. Krebs, MD

• Reimers, Daniel, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Daniel Reimers,

• Zhao, Yu, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Yu Zhao,

• Bartsch, Patricia, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany

Patricia Bartsch,

• Borchers, Alina, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany

Alina Borchers,

• Hellmig, Malte, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany

Malte Hellmig,

• Kilian, Christoph, UKE , Hamburg, Germany

Christoph Kilian,

• Enk, Leon U. B., Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany

Leon U. B. Enk,

• Riedel, Jan-Hendrik, UKE, Hamburg, Germany

Jan-Hendrik Riedel,

• Huber, Tobias B., University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Tobias B. Huber,

• Turner, Jan-Eric, University Medical Center Hamburg, Hamburg, Germany

Jan-Eric Turner,

• Panzer, Ulf, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Ulf Panzer,

• Mittrücker, Hans-willi, Institute for Immunology, Hamburg, Germany

Hans-willi Mittrücker,

Background

Tissue resident memory T (Trm) cells represent a new type of memory cells that reside in peripheral organs without recirculating. They provide rapid on-site immune protection against previous exposed pathogens. However, it remains to be clarified whether Trm cells also interfere with responses unrelated to the primary infection, such as organ-specific autoimmunity.

Methods

To study Trm cells, we used a combined approach of flow cytometry, histology and single cell RNA-sequencing. Human kidney tissue was obtained from tumour-nephrectomies. In mice, renal Th17 cells were induced by S. aureus infection. GN was induced with the nephrotoxic sheep serum or by immunisation with a fragment of the α3 chain of type IV collagen. We also used Listeria monocytogenes in another infection model.

Results

We found high frequencies of CD4⁺ CD69⁺ Trm cells of the Th17 phenotype, which we identified based on homology to published core transcriptional and protein data sets. We operationally named them Trm17 cells. CD4⁺ Th17 cells are involved in the response to major human pathogens such as S. aureus, and play a critical role in autoimmunity such as crescentic glomerulonephritis (cGN). We established a mouse model of S. aureus infection that resulted in initially high renal bacteria titres and a profound accumulation of Th17 cells in the kidney. Renal Th17 cells persist long-term (>100 days) after clearance of the infection, present with the phenotype of Trm cells and partially protect against re-infection. Induction of autoimmune kidney disease (cGN) in mice, which recovered from S. aureus infection, resulted in a more rapid and aggravated renal Th17 response and consequently developed a more severe course of cGN. By labelling renal cells in photoconvertible Kaede-transgenic mice, we were able to demonstrate that S. aureus induced Trm17 cells contribute significantly to the enhanced local IL-17 immune response in cGN.

Conclusion

Thus, pathogen-induced Trm17 cells in peripheral tissues are capable of rapidly responding to an antigenic unrelated challenge thereby driving renal autoimmune diseases. Our data suggest that Trm cells might have a previously unknown role in amplifying organ-specific autoimmunity.

Funding

• Government Support - Non-U.S.