Activated renal dendritic cells cross present intrarenal antigens after ischemia reperfusion injury

Sarah L L Snelgrove, Cecilia Lo, Pamela Hall, Camden Y Y Lo, Maliha A A Alikhan, Toby T. Coates, Stephen R R Holdsworth, Michael J J Hickey, Richard R. Kitching

Research output: Contribution to journalArticleResearchpeer-review

Abstract

BACKGROUND: The healthy kidney contains an extensive population of renal mononuclear phagocytes (RMPs), with substantial phenotypic and functional diversity. However, how this diverse population is affected by ischemia-reperfusion injury (IRI), an obligate part of renal transplantation, is not yet well understood. The aim of this study was to characterize the phenotypic and functional alterations in RMPs induced by IRI. 

METHODS: RMPs were studied 24 and 72 hours after 30 minutes of renal ischemia or sham operation. Kidneys were digested and the phenotypes of renal leukocyte populations were analyzed via flow cytometry. Multiphoton microscopy was used to image renal dendritic cells (DCs) in vivo using CD11c reporter mice. The capacity of renal DCs to present antigen was examined by assessment of proliferation of ovalbumin-specific T cells in RIP-mOVA mice following sham or IRI procedures. 

RESULTS: IRI induced influx of monocytes, DCs, macrophages and neutrophils into the kidney. Classification of RMP subpopulations based on CD11b/CD11c expression demonstrated that the RMPs that increased in response to IRI were predominantly newly-recruited monocyte-derived inflammatory DCs. In vivo multiphoton imaging of CD11c-EYFP mice revealed that intrarenal DCs exhibited increased number and activity of dendrites in the postischemic period. IRI also promoted DC-dependent cross-presentation of renal antigens to CD8 T cells in the draining lymph node. 

CONCLUSION: In response to renal IRI, RMP populations are skewed towards those derived from inflammatory monocyte precursors. In addition, renal DCs undergo functional activation, increasing their capacity to activate antigen-specific CD8 T cells in renal draining lymph nodes.

Original languageEnglish
Pages (from-to)1013-1024
Number of pages12
JournalTransplantation
Volume101
Issue number5
DOIs
Publication statusPublished - May 2017

Cite this

@article{b30329414747426aab9c5e116f780155,
title = "Activated renal dendritic cells cross present intrarenal antigens after ischemia reperfusion injury",
abstract = "BACKGROUND: The healthy kidney contains an extensive population of renal mononuclear phagocytes (RMPs), with substantial phenotypic and functional diversity. However, how this diverse population is affected by ischemia-reperfusion injury (IRI), an obligate part of renal transplantation, is not yet well understood. The aim of this study was to characterize the phenotypic and functional alterations in RMPs induced by IRI. METHODS: RMPs were studied 24 and 72 hours after 30 minutes of renal ischemia or sham operation. Kidneys were digested and the phenotypes of renal leukocyte populations were analyzed via flow cytometry. Multiphoton microscopy was used to image renal dendritic cells (DCs) in vivo using CD11c reporter mice. The capacity of renal DCs to present antigen was examined by assessment of proliferation of ovalbumin-specific T cells in RIP-mOVA mice following sham or IRI procedures. RESULTS: IRI induced influx of monocytes, DCs, macrophages and neutrophils into the kidney. Classification of RMP subpopulations based on CD11b/CD11c expression demonstrated that the RMPs that increased in response to IRI were predominantly newly-recruited monocyte-derived inflammatory DCs. In vivo multiphoton imaging of CD11c-EYFP mice revealed that intrarenal DCs exhibited increased number and activity of dendrites in the postischemic period. IRI also promoted DC-dependent cross-presentation of renal antigens to CD8 T cells in the draining lymph node. CONCLUSION: In response to renal IRI, RMP populations are skewed towards those derived from inflammatory monocyte precursors. In addition, renal DCs undergo functional activation, increasing their capacity to activate antigen-specific CD8 T cells in renal draining lymph nodes.",
author = "Snelgrove, {Sarah L L} and Cecilia Lo and Pamela Hall and Lo, {Camden Y Y} and Alikhan, {Maliha A A} and Coates, {Toby T.} and Holdsworth, {Stephen R R} and Hickey, {Michael J J} and Kitching, {Richard R.}",
year = "2017",
month = "5",
doi = "10.1097/TP.0000000000001427",
language = "English",
volume = "101",
pages = "1013--1024",
journal = "Transplantation",
issn = "0041-1337",
publisher = "LWW",
number = "5",

}

Activated renal dendritic cells cross present intrarenal antigens after ischemia reperfusion injury. / Snelgrove, Sarah L L; Lo, Cecilia; Hall, Pamela; Lo, Camden Y Y; Alikhan, Maliha A A; Coates, Toby T.; Holdsworth, Stephen R R; Hickey, Michael J J; Kitching, Richard R.

In: Transplantation, Vol. 101, No. 5, 05.2017, p. 1013-1024.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Activated renal dendritic cells cross present intrarenal antigens after ischemia reperfusion injury

AU - Snelgrove, Sarah L L

AU - Lo, Cecilia

AU - Hall, Pamela

AU - Lo, Camden Y Y

AU - Alikhan, Maliha A A

AU - Coates, Toby T.

AU - Holdsworth, Stephen R R

AU - Hickey, Michael J J

AU - Kitching, Richard R.

PY - 2017/5

Y1 - 2017/5

N2 - BACKGROUND: The healthy kidney contains an extensive population of renal mononuclear phagocytes (RMPs), with substantial phenotypic and functional diversity. However, how this diverse population is affected by ischemia-reperfusion injury (IRI), an obligate part of renal transplantation, is not yet well understood. The aim of this study was to characterize the phenotypic and functional alterations in RMPs induced by IRI. METHODS: RMPs were studied 24 and 72 hours after 30 minutes of renal ischemia or sham operation. Kidneys were digested and the phenotypes of renal leukocyte populations were analyzed via flow cytometry. Multiphoton microscopy was used to image renal dendritic cells (DCs) in vivo using CD11c reporter mice. The capacity of renal DCs to present antigen was examined by assessment of proliferation of ovalbumin-specific T cells in RIP-mOVA mice following sham or IRI procedures. RESULTS: IRI induced influx of monocytes, DCs, macrophages and neutrophils into the kidney. Classification of RMP subpopulations based on CD11b/CD11c expression demonstrated that the RMPs that increased in response to IRI were predominantly newly-recruited monocyte-derived inflammatory DCs. In vivo multiphoton imaging of CD11c-EYFP mice revealed that intrarenal DCs exhibited increased number and activity of dendrites in the postischemic period. IRI also promoted DC-dependent cross-presentation of renal antigens to CD8 T cells in the draining lymph node. CONCLUSION: In response to renal IRI, RMP populations are skewed towards those derived from inflammatory monocyte precursors. In addition, renal DCs undergo functional activation, increasing their capacity to activate antigen-specific CD8 T cells in renal draining lymph nodes.

AB - BACKGROUND: The healthy kidney contains an extensive population of renal mononuclear phagocytes (RMPs), with substantial phenotypic and functional diversity. However, how this diverse population is affected by ischemia-reperfusion injury (IRI), an obligate part of renal transplantation, is not yet well understood. The aim of this study was to characterize the phenotypic and functional alterations in RMPs induced by IRI. METHODS: RMPs were studied 24 and 72 hours after 30 minutes of renal ischemia or sham operation. Kidneys were digested and the phenotypes of renal leukocyte populations were analyzed via flow cytometry. Multiphoton microscopy was used to image renal dendritic cells (DCs) in vivo using CD11c reporter mice. The capacity of renal DCs to present antigen was examined by assessment of proliferation of ovalbumin-specific T cells in RIP-mOVA mice following sham or IRI procedures. RESULTS: IRI induced influx of monocytes, DCs, macrophages and neutrophils into the kidney. Classification of RMP subpopulations based on CD11b/CD11c expression demonstrated that the RMPs that increased in response to IRI were predominantly newly-recruited monocyte-derived inflammatory DCs. In vivo multiphoton imaging of CD11c-EYFP mice revealed that intrarenal DCs exhibited increased number and activity of dendrites in the postischemic period. IRI also promoted DC-dependent cross-presentation of renal antigens to CD8 T cells in the draining lymph node. CONCLUSION: In response to renal IRI, RMP populations are skewed towards those derived from inflammatory monocyte precursors. In addition, renal DCs undergo functional activation, increasing their capacity to activate antigen-specific CD8 T cells in renal draining lymph nodes.

UR - http://www.scopus.com/inward/record.url?scp=84982860070&partnerID=8YFLogxK

UR - http://www.ncbi.nlm.nih.gov/pubmed/27495751

U2 - 10.1097/TP.0000000000001427

DO - 10.1097/TP.0000000000001427

M3 - Article

VL - 101

SP - 1013

EP - 1024

JO - Transplantation

JF - Transplantation

SN - 0041-1337

IS - 5

ER -