Blocking CCL8-CCR8-Mediated Early Allograft Inflammation Improves Kidney Transplant Function.

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.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1681/asn.2022020139

Publication Info

Dangi, Anil, Irma Husain, Collin Z Jordan, Shuangjin Yu, Naveen Natesh, Xiling Shen, Jean Kwun, Xunrong Luo, et al. (2022). Blocking CCL8-CCR8-Mediated Early Allograft Inflammation Improves Kidney Transplant Function. Journal of the American Society of Nephrology : JASN, 33(10). p. ASN.2022020139. 10.1681/asn.2022020139 Retrieved from https://hdl.handle.net/10161/26153.

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Scholars@Duke

Husain

Irma Husain

Assistant Professor of Medicine
Shen

Xiling Shen

Adjunct Professor in the Department of Pathology

Dr. Shen’s research interests lie at precision medicine and systems biology. His lab integrates engineering, computational and biological techniques to study cancer, stem cells, microbiota and the nervous system in the gut. This multidisciplinary work has been instrumental in initiating several translational clinical trials in precision therapy. He is the director of the Woo Center for Big Data and Precision Health (DAP) and a core member of the Center for Genomics and Computational Biology (GCB).

Luo

Xunrong Luo

Boyce Haller Distinguished Professor in Nephrology

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