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Updated: May 24, 2025
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Published on: July 13, 2019
The CXCR6-CXCL16 axis mediates T cell control of polyomavirus infection in the kidney
Matthew D Lauver1, Zoe E Katz1, Havell Markus2
1Department of Microbiology and Immunology, Penn State College of Medicine, Hershey, Pennsylvania, United States of America.
Abstract:
BK polyomavirus (PyV) establishes lifelong asymptomatic infections in the reno-urinary system of most humans. BKPyV-associated nephropathy is the leading infectious cause of kidney allograft loss. Using mouse PyV, a natural murine pathogen that also persists in the kidney, we define a dominant chemokine receptor-chemokine axis that directs T cell infiltration of the kidney. We found that CXCR6 was required for CD4+ and CD8+ T cells to be recruited to and retained in the kidney, respectively. Absence of CXCR6 impaired virus control in the kidney. The soluble form of CXCL16 was increased in kidneys of infected mice and in vivo CXCL16 neutralization reduced numbers of virus-specific CD8+ T cells infiltrating the kidney. In vivo administration of IL-12 upregulated CXCR6 expression on virus-specific CD8+ T cells, improved T cell recruitment to the infected kidney, and reduced virus levels. Notably, T cells in kidney biopsies from PyV-associated nephropathy patients express CXCR6 and transcriptional analysis shows significant upregulation of CXCR6 and CXCL16. These findings demonstrate the importance of the CXCR6-CXCL16 axis in regulating T cell responses in the kidney to PyV infection.
Insights
The CXCR6-CXCL16 axis is crucial for T cell kidney infiltration during polyomavirus infection. Targeting this pathway may improve kidney transplant outcomes by enhancing immune control.
Area of Science:
- Immunology
- Virology
- Nephrology
Background:
- BK polyomavirus (PyV) causes lifelong kidney infections and is a leading cause of kidney transplant failure.
- Understanding T cell responses in the kidney is vital for managing PyV infections and allograft survival.
Purpose of the Study:
- To define the chemokine receptor-chemokine axis regulating T cell infiltration in the kidney during PyV infection.
- To investigate the role of CXCR6 and CXCL16 in T cell responses to PyV.
Main Methods:
- Utilized a mouse polyomavirus (PyV) infection model.
- Assessed T cell recruitment and retention using CXCR6 knockout mice.
- Administered CXCL16 neutralizing antibodies and IL-12.
- Analyzed kidney biopsies from PyV-associated nephropathy patients.
Main Results:
- CXCR6 is essential for CD4+ and CD8+ T cell recruitment and retention in the infected kidney.
- CXCL16 neutralization reduced virus-specific CD8+ T cell infiltration.
- IL-12 treatment enhanced CXCR6 expression, T cell recruitment, and viral control.
- CXCR6 and CXCL16 were upregulated in kidney biopsies from PyV-associated nephropathy patients.
Conclusions:
- The CXCR6-CXCL16 axis is a key regulator of T cell responses in the kidney during PyV infection.
- This axis is relevant in human PyV-associated nephropathy, suggesting therapeutic potential.
