Th1/17 Cells Infiltrate Murine Cytomegalovirus-Infected Renal Allografts via Virus-Induced CCL20 and Promote Th1 Cells through IL-17A
Th1/17 Cells Infiltrate Murine Cytomegalovirus-Infected Renal Allografts via Virus-Induced CCL20 and Promote Th1 Cells through IL-17A
ABSTRACT Cytomegalovirus (CMV) infection is associated with renal allograft failure by unknown mechanisms. In a murine renal transplant model, murine CMV (MCMV) induces intragraft infiltration of Th17 cells co-expressing Th1 cytokines, IFN-γ and TNF-α, but only a minority of intragraft Th17 cells are specific for MCMV antigens. Instead, MCMV promotes viral antigen-independent Th17 cell recruitment via CCL20-CCR6 and CXCL10-CXCR3 interactions. Th17 cells correlate directly with Th1 cell frequencies and inversely with Tregs in MCMV infected grafts. Pharmacologic inhibition of IL-17A reduces intragraft Th17 cells and neutrophils, increases Tregs, and reduces total but not MCMV-specific Th1 cells. Among a clinical renal transplant cohort with acute rejection, patients with CMV DNAemia had significantly higher serum IL-17A quantities compared to those without CMV DNAemia. Together, these findings indicate that CMV infection upregulates Th17 cell activity during acute rejection and suggests that inhibition of IL-17A may ameliorate CMV-associated allograft injury without impairing antiviral Th1 cells.
Shimamura Masako、Zeng Qiang、Velazquez Victoria M.、Fitch James R.、Boddeda Srinivasa R.、Sharma Ashish、Anand Shashi、Dhital Ravi、Minz Ranjana W.、Cianciolo Rachel、Minz Mukut
Center for Vaccines and Immunity, The Abigail Wexner Research Institute, Nationwide Children?ˉs Hospital||Division of Pediatric Infectious Diseases, Department of Pediatrics, College of Medicine, The Ohio State UniversityCenter for Cardiovascular Research, The Abigail Research Institute, Nationwide Children?ˉs HospitalCenter for Vaccines and Immunity, The Abigail Wexner Research Institute, Nationwide Children?ˉs HospitalThe Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children?ˉs HospitalCenter for Vaccines and Immunity, The Abigail Wexner Research Institute, Nationwide Children?ˉs HospitalDepartment of Renal Transplant Surgery, Post- Graduate Institute of Medical Education and ResearchDepartment of Immunopathology, Post Graduate Institute of Medical Education and ResearchCenter for Vaccines and Immunity, The Abigail Wexner Research Institute, Nationwide Children?ˉs HospitalDepartment of Immunopathology, Post Graduate Institute of Medical Education and ResearchDepartment of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State UniversityDepartment of Renal Transplant Surgery, Post- Graduate Institute of Medical Education and Research
基础医学
Shimamura Masako,Zeng Qiang,Velazquez Victoria M.,Fitch James R.,Boddeda Srinivasa R.,Sharma Ashish,Anand Shashi,Dhital Ravi,Minz Ranjana W.,Cianciolo Rachel,Minz Mukut.Th1/17 Cells Infiltrate Murine Cytomegalovirus-Infected Renal Allografts via Virus-Induced CCL20 and Promote Th1 Cells through IL-17A[EB/OL].(2025-03-28)[2025-05-16].https://www.biorxiv.org/content/10.1101/2021.08.05.455061.点此复制
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