IL-27Rα: A Novel Molecular Imaging Marker for Allograft Rejection

Int J Mol Sci. 2020 Feb 15;21(4):1315. doi: 10.3390/ijms21041315.

Abstract

Non-invasively monitoring allogeneic graft rejection with a specific marker is of great importance for prognosis of patients. Recently, data revealed that IL-27Rα was up-regulated in alloreactive CD4+ T cells and participated in inflammatory diseases. Here, we evaluated whether IL-27Rα could be used in monitoring allogeneic graft rejection both in vitro and in vivo. Allogeneic (C57BL/6 donor to BALB/c recipient) and syngeneic (BALB/c both as donor and recipient) skin grafted mouse models were established. The expression of IL-27Rα in grafts was detected. The radio-probe, 125I-anti-IL-27Rα mAb, was prepared. Dynamic whole-body phosphor-autoradiography, ex vivo biodistribution and immunofluorescence staining were performed. The results showed that the highest expression of IL-27Rα was detected in allogeneic grafts on day 10 post transplantation (top period of allorejection). 125I-anti-IL-27Rα mAb was successfully prepared with higher specificity and affinity. Whole-body phosphor-autoradiography showed higher radioactivity accumulation in allogeneic grafts than syngeneic grafts on day 10. The uptake of 125I-anti-IL-27Rα mAb in allogeneic grafts could be almost totally blocked by pre-injection with excess unlabeled anti-IL-27Rα mAb. Interestingly, we found that 125I-anti-IL-27Rα mAb accumulated in allogeneic grafts, along with weaker inflammation earlier on day 6. The high uptake of 125I-anti-IL-27Rα mAb was correlated with the higher infiltrated IL-27Rα positive cells (CD3+/CD68+) in allogeneic grafts. In conclusion, IL-27Rα may be a novel molecular imaging marker to predict allorejection.

Keywords: IL-27Rα 1; allorejection 2; autoradiography imaging 3; biomarker 4; radioiodine 5.

MeSH terms

  • Allografts
  • Animals
  • Antibodies, Monoclonal / immunology
  • Biomarkers / metabolism*
  • Gene Expression Regulation, Developmental / genetics
  • Graft Rejection / genetics*
  • Graft Rejection / immunology
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Molecular Imaging*
  • Receptors, Interleukin / genetics*
  • Receptors, Interleukin / isolation & purification
  • Receptors, Interleukin / metabolism
  • Skin Transplantation / adverse effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Tissue Distribution / immunology
  • Transplantation, Homologous

Substances

  • Antibodies, Monoclonal
  • Biomarkers
  • Il27ra protein, mouse
  • Receptors, Interleukin