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.

We used an allogeneic murine kidney transplant model in which CD45.2 BALB/c kidneys were transplanted to CD45.1 C57BL/6 recipients.

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 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.

Targeting the CCL8-CCR8 axis is a promising measure to reduce early kidney allograft inflammation.

在肾移植中，早期同种异体移植物炎症会损害长期同种异体移植物功能。然而，早期肾同种异体移植炎症的精确介导因素尚不清楚，这使得设计治疗干预措施具有挑战性。

我们使用同种异体小鼠肾移植模型，其中 CD45.2 BALB/c 肾脏被移植到 CD45.1 C57BL/6 受体中。

同种异体移植物内的供体肾常驻巨噬细胞在前 3 天内迅速扩增。在此期间，它们还被诱导表达高水平的Ccl8，这反过来又促进受体单核细胞移植物浸润、分化为常驻巨噬细胞以及随后的Ccl8表达。随后受体 CCR8 ⁺ T 细胞的移植物浸润增强，包括 CD4、CD8 和T细胞。因此，阻断 CCL8-CCR8 或消耗供体肾脏驻留巨噬细胞可显着抑制早期同种异体移植免疫细胞浸润并促进卓越的短期同种异体移植功能。

靶向 CCL8-CCR8 轴是减少早期肾同种异体移植炎症的一种有前途的措施。