TY - JOUR
T1 - Ischemia Reperfusion Injury Triggers CXCL13 Release and B-Cell Recruitment After Allogenic Kidney Transplantation
AU - Kreimann, Kirill
AU - Jang, Mi Sun
AU - Rong, Song
AU - Greite, Robert
AU - von Vietinghoff, Sibylle
AU - Schmitt, Roland
AU - Bräsen, Jan Hinrich
AU - Schiffer, Lena
AU - Gerstenberg, Jessica
AU - Vijayan, Vijith
AU - Dittrich-Breiholz, Oliver
AU - Wang, Li
AU - Karsten, Christian M.
AU - Gwinner, Wilfried
AU - Haller, Hermann
AU - Immenschuh, Stephan
AU - Gueler, Faikah
N1 - Funding Information:
We thank Herle Chlebusch, Heike L?hrs, and Michaela Beese for excellent technical support. We thank Dr. Alexandra Helmke and Dr. Payel Sen for great experimental support in single-cell RNA sequencing. We thank Dr. Michael Brownstein for editing the manuscript. Funding. This study was supported by the Deutsche Forschungsgemeinschaft (DFG) grant GU 613/1-1 to FG and grant IM 20/4-1 to SI.
Publisher Copyright:
© Copyright © 2020 Kreimann, Jang, Rong, Greite, von Vietinghoff, Schmitt, Bräsen, Schiffer, Gerstenberg, Vijayan, Dittrich-Breiholz, Wang, Karsten, Gwinner, Haller, Immenschuh and Gueler.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/8/6
Y1 - 2020/8/6
N2 - Ischemia reperfusion injury (IRI) is linked with inflammation in kidney transplantation (ktx). The chemokine CXCL13, also known as B lymphocyte chemoattractant, mediates recruitment of B cells within follicles of lymphoid tissues and has recently been identified as a biomarker for acute kidney allograft rejection. The goal of this study was to explore whether IRI contributes to the up-regulation of CXCL13 levels in ktx. It is demonstrated that systemic levels of CXCL13 were increased in mouse models of uni- and bilateral renal IRI, which correlated with the duration of IRI. Moreover, in unilateral renal IRI CXCL13 expression in ischemic kidneys was up-regulated. Immunohistochemical studies revealed infiltration of CD22+ B-cells and, single-cell RNA sequencing analysis a higher number of cells expressing the CXCL13 receptor CXCR5, in ischemic kidneys 7 days post IRI, respectively. The potential relevance of these findings was also evaluated in a mouse model of ktx. Increased levels of serum CXCL13 correlated with the lengths of cold ischemia times and were further enhanced in allogenic compared to isogenic kidney transplants. Taken together, these findings indicate that IRI is associated with increased systemic levels of CXCL13 in renal IRI and ktx.
AB - Ischemia reperfusion injury (IRI) is linked with inflammation in kidney transplantation (ktx). The chemokine CXCL13, also known as B lymphocyte chemoattractant, mediates recruitment of B cells within follicles of lymphoid tissues and has recently been identified as a biomarker for acute kidney allograft rejection. The goal of this study was to explore whether IRI contributes to the up-regulation of CXCL13 levels in ktx. It is demonstrated that systemic levels of CXCL13 were increased in mouse models of uni- and bilateral renal IRI, which correlated with the duration of IRI. Moreover, in unilateral renal IRI CXCL13 expression in ischemic kidneys was up-regulated. Immunohistochemical studies revealed infiltration of CD22+ B-cells and, single-cell RNA sequencing analysis a higher number of cells expressing the CXCL13 receptor CXCR5, in ischemic kidneys 7 days post IRI, respectively. The potential relevance of these findings was also evaluated in a mouse model of ktx. Increased levels of serum CXCL13 correlated with the lengths of cold ischemia times and were further enhanced in allogenic compared to isogenic kidney transplants. Taken together, these findings indicate that IRI is associated with increased systemic levels of CXCL13 in renal IRI and ktx.
UR - http://www.scopus.com/inward/record.url?scp=85089802049&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2020.01204
DO - 10.3389/fimmu.2020.01204
M3 - Journal articles
C2 - 32849490
AN - SCOPUS:85089802049
SN - 1664-3224
VL - 11
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 1204
ER -
