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Live Images of Donor Dendritic Cells Trafficking via CX3CR1 Pathway
Takuya Ueno1, Pilhan Kim2, Martina M McGrath1
1Renal Division, Transplantation Research Center, Brigham and Women's Hospital, Harvard Medical School , Boston, MA , USA.
Insights
CX3CR1 signaling impacts dendritic cell (DC) migration in heart transplants. Post-transplant, DCs change shape and enter circulation, with limited migration to lymphoid tissues observed.
Area of Science:
- Immunology
- Transplantation Biology
- Cellular Trafficking
Background:
- CX3CR1 (chemokine receptor) is crucial for monocyte migration and dendritic cell (DC) differentiation.
- The role of chemokine pathways in DC homeostasis within heart transplants is unknown.
- Previous work showed CX3CR1-deficient donors improve heart allograft survival.
Purpose of the Study:
- To investigate the in vivo trafficking of dendritic cells (dDCs) in a heart transplant model.
- To utilize a novel imaging tool to track CX3CR1-GFP+ DCs in a heart allograft.
Main Methods:
- Development and application of a novel in vivo imaging tool.
- Tracking of CX3CR1-GFP+ DCs in a heart graft transplanted into BALB/c recipients.
- Analysis of GFP+ cell distribution and morphology at 3, 24, and 72 hours post-transplant.
Main Results:
- GFP+ cells were initially found within cardiac myocytes, undergoing morphological changes (stretching) within hours.
- By 72 hours, most GFP+ cells migrated to vessel areas near the vessel wall.
- Very few GFP+ cells (one) were detected in draining lymph nodes (mesenteric and inguinal).
Conclusions:
- Post-transplant, dendritic cells (dDCs) exhibit immediate morphological changes and exit the organ via circulation.
- While dDCs remain in transplanted organs, their migration to lymphoid tissues requires further investigation.
Background:
A number of studies have demonstrated the role of CX3CR1 in regulating the migration of monocytes into peripheral tissue and their transformation into dendritic cell (DC). No data are yet available on the importance of chemokine pathways in regulating homeostasis of DC in heart transplants. Recently, we showed that recipients of heart allografts from CX3CR1-/- donors show longer survival. To assess the trafficking of dDC, we have developed and tested a novel in vivo imaging tool in CX3CR1GFP/+ DC (B6 background) heart graft into BALB/c recipient model.
Results:
Majority of GFP+ cells were noted in the middle of cardiac myocyte. However few hours post transplant, they experienced morphological changes including stretching their extensions (3 and 24 h). However, images from 72 h at cardiac graft showed many of GFP+ cells moved to vessel areas. GFP+ cells were detected in near vessel wall. Only one GFP+ cell was observed in three lymph nodes (two mesenteric and one inguinal) (72 h).
Conclusion:
Our data indicate that immediately post transplant dDC undergo morphological changes and traffic out of the organs via systemic circulation. While, we still noted presence of dDC in the transplanted organs, their trafficking to lymphoid tissue remains to be fully explored.
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