Kidney Week

Abstract: FR-OR37

T Cell Egress from the Kidney to the Renal Lymph Node Is Regulated by Their Activation State and Controls Tissue Inflammation

Session Information

• Glomerular Diseases: Mechanisms and More
  October 25, 2024 | Location: Room 1, Convention Center
  Abstract Time: 04:30 PM - 04:40 PM

Category: Glomerular Diseases

• 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

• Engesser, Jonas, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Hamburg, Germany

Jonas Engesser, DrMed

• Riedel, Jan-Hendrik, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Hamburg, Germany

Jan-Hendrik Riedel, MD

• Asada, Nariaki, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Hamburg, Germany

Nariaki Asada, MD, PhD

• Paust, Hans-Joachim, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Hamburg, Germany

Hans-Joachim Paust, PhD

• Khatri, Robin, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Hamburg, Germany

Robin Khatri

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

Zeba Sultana

• Meyer-Schwesinger, Catherine, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Hamburg, Germany

Catherine Meyer-Schwesinger, MD

• Wiech, Thorsten, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Hamburg, Germany

Thorsten Wiech, DrMed

• Puelles, Victor G., Universitatsklinikum Hamburg-Eppendorf, Hamburg, Hamburg, Germany

Victor G. Puelles, MD, PhD

• Bonn, Stefan, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Hamburg, Germany

Stefan Bonn, PhD

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

Christian F. Krebs, MD

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

Ulf Panzer, MD

Background

A hallmark of autoimmune diseases such as crescentic glomerulonephritis (cGN) is the infiltration of pathogenic leukocytes into the kidney. Here, especially CD4⁺ T cells play a key role in orchestrating the immune response and driving tissue damage. While T cell infiltration is described well, little is known about T cell emigration out of the kidney via lymph vessels and its role in controlling tissue inflammation. In this study, we aim to decipher T cell emigration signals and their role on tissue injury.

Methods

Human kidney biopsies from ANCA glomerulonephritis (ANCA-GN) patients were analyzed using 3D-immunofluorescence of lymphatics, and combined scRNA-seq and spatial transcriptome analysis. To investigate the trafficking of T cells from the kidney to the draining lymph node, we developed a new experimental system using the photoconvertible Kaede mouse. Using this system, we labelled renal T cells by photoconversion and analyzed their in vivo migration under homeostatic and nephritic conditions (experimental cGN).

Results

In ANCA-GN, lymphangiogenesis was primarily observed in the inflamed areas, accompanied by a predominance of CD4⁺ T cells and macrophages. However, during inflammation, only T cells emigrated out of the kidney via afferent lymphatics. To elucidate the mechanisms regulating T cell egress, we used our Kaede-mouse model to identify differential expression of the chemokine receptors CXCR6 and S1PR1 in emigrated vs. resident cells. T cell activation was linked to CXCR6 upregulation and tissue retention, while loss of activation led to CXCR6 downregulation, S1PR1 upregulation, and tissue egress. Blocking S1PR1 signaling exacerbated tissue damage by increasing T cell retention. Finally, flow cytometry and scRNA-seq analysis of human kidney, blood, and lymph fluid confirmed our observations from the murine model, including the downregulation of activation markers in tissue-emigrated T cells.

Conclusion

T cell emigration from the kidney to the renal lymph node is regulated by T cell activation signals and controls tissue inflammation and resolution. These data indicate that strategies to promote T cell egress offer potential options for treating immune mediated kidney diseases.

Funding

• Government Support – Non-U.S.