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Updated: Sep 1, 2025
Mouse Kidney Transplantation: Models of Allograft Rejection
Published on: October 11, 2014
Blocking CCL8-CCR8-Mediated Early Allograft Inflammation Improves Kidney Transplant Function
Anil Dangi1, Irma Husain1, Collin Z Jordan1
1Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina.
Background:
In kidney transplantation, early allograft inflammation impairs long-term allograft function. However, precise mediators of early kidney allograft inflammation are unclear, making it challenging to design therapeutic interventions.
Methods:
We used an allogeneic murine kidney transplant model in which CD45.2 BALB/c kidneys were transplanted to CD45.1 C57BL/6 recipients.
Results:
Donor kidney resident macrophages within the allograft expanded rapidly in the first 3 days. During this period, they were also induced to express a high level of Ccl8, which, in turn, promoted recipient monocyte graft infiltration, their differentiation to resident macrophages, and subsequent expression of Ccl8. Enhanced graft infiltration of recipient CCR8+ T cells followed, including CD4, CD8, and γδ T cells. Consequently, blocking CCL8-CCR8 or depleting donor kidney resident macrophages significantly inhibits early allograft immune cell infiltration and promotes superior short-term allograft function.
Conclusions:
Targeting the CCL8-CCR8 axis is a promising measure to reduce early kidney allograft inflammation.
Insights
Early kidney transplant inflammation involves donor macrophages expressing CCL8, attracting recipient monocytes and T cells. Blocking this CCL8-CCR8 interaction or depleting macrophages improves early allograft function.
Area of Science:
- Immunology
- Transplantation Biology
- Renal Medicine
Background:
- Early allograft inflammation in kidney transplantation negatively impacts long-term graft survival.
- Identifying specific mediators of early kidney allograft inflammation is crucial for developing targeted therapies.
Purpose of the Study:
- To elucidate the key cellular and molecular players driving early inflammation in kidney allografts.
- To evaluate the therapeutic potential of targeting identified inflammatory mediators.
Main Methods:
- Utilized an allogeneic murine kidney transplant model.
- Investigated the role of donor kidney resident macrophages and the CCL8-CCR8 axis in early allograft response.
Main Results:
- Donor kidney resident macrophages rapidly expanded and expressed high levels of CCL8 within 3 days post-transplant.
- CCL8 promoted recipient monocyte infiltration and differentiation into macrophages, further increasing CCL8 expression.
- CCL8-CCR8 interaction led to enhanced infiltration of recipient T cells (CD4, CD8, γδ).
- Blocking CCL8-CCR8 or depleting donor macrophages significantly reduced immune cell infiltration and improved short-term allograft function.
Conclusions:
- The CCL8-CCR8 signaling pathway is a critical driver of early kidney allograft inflammation.
- Targeting the CCL8-CCR8 axis represents a promising therapeutic strategy to mitigate early post-transplant inflammation and enhance graft outcomes.
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