Blocking CCL8-CCR8-Mediated Early Allograft Inflammation Improves Kidney Transplant Function.
J Am Soc Nephrol
; 33(10): 1876-1890, 2022 10.
Article
em En
| MEDLINE
| ID: mdl-35973731
ABSTRACT
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.Palavras-chave
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Base de dados:
MEDLINE
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Transplante de Rim
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article