阻断 CCL8-CCR8 介导的早期移植物炎症可改善肾移植功能。
Blocking CCL8-CCR8-Mediated Early Allograft Inflammation Improves Kidney Transplant Function.
机构信息
Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina.
Division of Organ Transplantation, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
出版信息
J Am Soc Nephrol. 2022 Oct;33(10):1876-1890. doi: 10.1681/ASN.2022020139. Epub 2022 Aug 16.
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 , which, in turn, promoted recipient monocyte graft infiltration, their differentiation to resident macrophages, and subsequent expression of . 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.
CONCLUSIONS
Targeting the CCL8-CCR8 axis is a promising measure to reduce early kidney allograft inflammation.
背景
在肾移植中，早期同种异体移植物炎症会损害长期移植物功能。然而，早期肾同种异体移植炎症的确切介质尚不清楚，这使得设计治疗干预措施具有挑战性。
方法
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。
结果
供体肾固有巨噬细胞在移植物中迅速扩增，在最初的 3 天内。在此期间，它们也被诱导表达高水平的 ，这反过来又促进了受体单核细胞移植物浸润，它们分化为固有巨噬细胞，并随后表达 。随后，受体 CCR8 T 细胞（包括 CD4、CD8 和 T 细胞）增强了移植物浸润。因此，阻断 CCL8-CCR8 或耗尽供体肾固有巨噬细胞可显著抑制早期同种异体免疫细胞浸润，并促进短期移植物功能改善。
结论
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。
Zotero 插件