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

Publication ,  Journal Article
Dangi, A; Husain, I; Jordan, CZ; Yu, S; Natesh, N; Shen, X; Kwun, J; Luo, X
Published in: J Am Soc Nephrol
October 2022

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.

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Published In

J Am Soc Nephrol

DOI

EISSN

1533-3450

Publication Date

October 2022

Volume

33

Issue

10

Start / End Page

1876 / 1890

Location

United States

Related Subject Headings

  • Urology & Nephrology
  • Transplantation, Homologous
  • Receptors, CCR8
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C
  • Mice
  • Kidney Transplantation
  • Inflammation
  • Graft Survival
  • Graft Rejection
 

Citation

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Dangi, A., Husain, I., Jordan, C. Z., Yu, S., Natesh, N., Shen, X., … Luo, X. (2022). Blocking CCL8-CCR8-Mediated Early Allograft Inflammation Improves Kidney Transplant Function. J Am Soc Nephrol, 33(10), 1876–1890. https://doi.org/10.1681/ASN.2022020139
Dangi, Anil, Irma Husain, Collin Z. Jordan, Shuangjin Yu, Naveen Natesh, Xiling Shen, Jean Kwun, and Xunrong Luo. “Blocking CCL8-CCR8-Mediated Early Allograft Inflammation Improves Kidney Transplant Function.J Am Soc Nephrol 33, no. 10 (October 2022): 1876–90. https://doi.org/10.1681/ASN.2022020139.
Dangi A, Husain I, Jordan CZ, Yu S, Natesh N, Shen X, et al. Blocking CCL8-CCR8-Mediated Early Allograft Inflammation Improves Kidney Transplant Function. J Am Soc Nephrol. 2022 Oct;33(10):1876–90.
Dangi, Anil, et al. “Blocking CCL8-CCR8-Mediated Early Allograft Inflammation Improves Kidney Transplant Function.J Am Soc Nephrol, vol. 33, no. 10, Oct. 2022, pp. 1876–90. Pubmed, doi:10.1681/ASN.2022020139.
Dangi A, Husain I, Jordan CZ, Yu S, Natesh N, Shen X, Kwun J, Luo X. Blocking CCL8-CCR8-Mediated Early Allograft Inflammation Improves Kidney Transplant Function. J Am Soc Nephrol. 2022 Oct;33(10):1876–1890.

Published In

J Am Soc Nephrol

DOI

EISSN

1533-3450

Publication Date

October 2022

Volume

33

Issue

10

Start / End Page

1876 / 1890

Location

United States

Related Subject Headings

  • Urology & Nephrology
  • Transplantation, Homologous
  • Receptors, CCR8
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C
  • Mice
  • Kidney Transplantation
  • Inflammation
  • Graft Survival
  • Graft Rejection