Kidney resident macrophages have distinct subsets and multifunctional roles

Christine Chew; Oliver J Brand; Tomohiko Yamamura; Craig Lawless; Mychel Raony Paiva Teixeira Morais; Leo Zeef; I-Hsuan Lin; Gareth Howell; Sylvia Lui; Franziska Lausecker; Christopher Jagger; Tovah N Shaw; Siddharth Krishnan; Flora A McClure; Hayley Bridgeman; Kelly Wemyss; Joanne E Konkel; Tracy Hussell; Rachel Lennon

doi:10.1016/j.matbio.2024.02.002

Kidney resident macrophages have distinct subsets and multifunctional roles

Christine Chew, Oliver J Brand, Tomohiko Yamamura, Craig Lawless, Mychel Raony Paiva Teixeira Morais, Leo Zeef, I-Hsuan Lin, Gareth Howell, Sylvia Lui, Franziska Lausecker, Christopher Jagger, Tovah N Shaw, Siddharth Krishnan, Flora A McClure, Hayley Bridgeman, Kelly Wemyss, Joanne E Konkel, Tracy Hussell, Rachel Lennon

School of Biological Sciences

Research output: Contribution to journal › Article › peer-review

Abstract

Background
The kidney contains distinct glomerular and tubulointerstitial compartments with diverse cell types and extracellular matrix components. The role of immune cells in glomerular environment is crucial for dampening inflammation and maintaining homeostasis. Macrophages are innate immune cells that are influenced by their tissue microenvironment. However, the multifunctional role of kidney macrophages remains unclear.
Methods
Flow and imaging cytometry were used to determine the relative expression of CD81 and CX3CR1 (C-X3-C motif chemokine receptor 1) in kidney macrophages. Monocyte replenishment was assessed in Cx3cr1CreER X R26-yfp-reporter and shielded chimeric mice. Bulk RNA-sequencing and mass spectrometry-based proteomics were performed on isolated kidney macrophages from wild type and Col4a5−/− (Alport) mice. RNAscope was used to visualize transcripts and macrophage purity in bulk RNA assessed by CIBERSORTx analyses.
Results
In wild type mice we identified three distinct kidney macrophage subsets using CD81 and CX3CR1 and these subsets showed dependence on monocyte replenishment. In addition to their immune function, bulk RNA-sequencing of macrophages showed enrichment of biological processes associated with extracellular matrix. Proteomics identified collagen IV and laminins in kidney macrophages from wild type mice whilst other extracellular matrix proteins including cathepsins, ANXA2 and LAMP2 were enriched in Col4a5−/− (Alport) mice. A subset of kidney macrophages co-expressed matrix and macrophage transcripts.
Conclusions
We identified CD81 and CX3CR1 positive kidney macrophage subsets with distinct dependence for monocyte replenishment. Multiomic analysis demonstrated that these cells have diverse functions that underscore the importance of macrophages in kidney health and disease.

Original language	English
Pages (from-to)	23-37
Number of pages	15
Journal	Matrix Biology
Volume	127
Early online date	7 Feb 2024
DOIs	https://doi.org/10.1016/j.matbio.2024.02.002
Publication status	Published - Mar 2024

Keywords / Materials (for Non-textual outputs)

Kidney
Macrophages
Basement membrane
Extracellular matrix
Cytometry
RNA-sequencing
Proteomics

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10.1016/j.matbio.2024.02.002

1-s2.0-S0945053X24000210-mainFinal published version, 10.8 MBLicence: CC BY

https://www.sciencedirect.com/science/article/pii/S0945053X24000210

Cite this

Chew, C., Brand, O. J., Yamamura, T., Lawless, C., Morais, M. R. P. T., Zeef, L., Lin, I.-H., Howell, G., Lui, S., Lausecker, F., Jagger, C., Shaw, T. N., Krishnan, S., McClure, F. A., Bridgeman, H., Wemyss, K., Konkel, J. E., Hussell, T., & Lennon, R. (2024). Kidney resident macrophages have distinct subsets and multifunctional roles. Matrix Biology, 127, 23-37. https://doi.org/10.1016/j.matbio.2024.02.002

@article{0f18454caf75432cbfa86ec50603146c,

title = "Kidney resident macrophages have distinct subsets and multifunctional roles",

abstract = "Background The kidney contains distinct glomerular and tubulointerstitial compartments with diverse cell types and extracellular matrix components. The role of immune cells in glomerular environment is crucial for dampening inflammation and maintaining homeostasis. Macrophages are innate immune cells that are influenced by their tissue microenvironment. However, the multifunctional role of kidney macrophages remains unclear. Methods Flow and imaging cytometry were used to determine the relative expression of CD81 and CX3CR1 (C-X3-C motif chemokine receptor 1) in kidney macrophages. Monocyte replenishment was assessed in Cx3cr1CreER X R26-yfp-reporter and shielded chimeric mice. Bulk RNA-sequencing and mass spectrometry-based proteomics were performed on isolated kidney macrophages from wild type and Col4a5−/− (Alport) mice. RNAscope was used to visualize transcripts and macrophage purity in bulk RNA assessed by CIBERSORTx analyses. Results In wild type mice we identified three distinct kidney macrophage subsets using CD81 and CX3CR1 and these subsets showed dependence on monocyte replenishment. In addition to their immune function, bulk RNA-sequencing of macrophages showed enrichment of biological processes associated with extracellular matrix. Proteomics identified collagen IV and laminins in kidney macrophages from wild type mice whilst other extracellular matrix proteins including cathepsins, ANXA2 and LAMP2 were enriched in Col4a5−/− (Alport) mice. A subset of kidney macrophages co-expressed matrix and macrophage transcripts. Conclusions We identified CD81 and CX3CR1 positive kidney macrophage subsets with distinct dependence for monocyte replenishment. Multiomic analysis demonstrated that these cells have diverse functions that underscore the importance of macrophages in kidney health and disease.",

keywords = "Kidney, Macrophages, Basement membrane, Extracellular matrix, Cytometry, RNA-sequencing, Proteomics",

author = "Christine Chew and Brand, \{Oliver J\} and Tomohiko Yamamura and Craig Lawless and Morais, \{Mychel Raony Paiva Teixeira\} and Leo Zeef and I-Hsuan Lin and Gareth Howell and Sylvia Lui and Franziska Lausecker and Christopher Jagger and Shaw, \{Tovah N\} and Siddharth Krishnan and McClure, \{Flora A\} and Hayley Bridgeman and Kelly Wemyss and Konkel, \{Joanne E\} and Tracy Hussell and Rachel Lennon",

note = "We thank staff from the bioimaging, histology, flow cytometry, genomic technologies, bioinformatics, mass spectrometry core facilities, the biological service facilities and Epistem Ltd (irradiation facilities). We also thank Stefano Rossi for his help with data analysis for the initial submission.",

year = "2024",

month = mar,

doi = "10.1016/j.matbio.2024.02.002",

language = "English",

volume = "127",

pages = "23--37",

journal = "Matrix Biology",

issn = "0945-053X",

publisher = "Elsevier",

}

Chew, C, Brand, OJ, Yamamura, T, Lawless, C, Morais, MRPT, Zeef, L, Lin, I-H, Howell, G, Lui, S, Lausecker, F, Jagger, C, Shaw, TN, Krishnan, S, McClure, FA, Bridgeman, H, Wemyss, K, Konkel, JE, Hussell, T & Lennon, R 2024, 'Kidney resident macrophages have distinct subsets and multifunctional roles', Matrix Biology, vol. 127, pp. 23-37. https://doi.org/10.1016/j.matbio.2024.02.002

TY - JOUR

T1 - Kidney resident macrophages have distinct subsets and multifunctional roles

AU - Chew, Christine

AU - Brand, Oliver J

AU - Yamamura, Tomohiko

AU - Lawless, Craig

AU - Morais, Mychel Raony Paiva Teixeira

AU - Zeef, Leo

AU - Lin, I-Hsuan

AU - Howell, Gareth

AU - Lui, Sylvia

AU - Lausecker, Franziska

AU - Jagger, Christopher

AU - Shaw, Tovah N

AU - Krishnan, Siddharth

AU - McClure, Flora A

AU - Bridgeman, Hayley

AU - Wemyss, Kelly

AU - Konkel, Joanne E

AU - Hussell, Tracy

AU - Lennon, Rachel

N1 - We thank staff from the bioimaging, histology, flow cytometry, genomic technologies, bioinformatics, mass spectrometry core facilities, the biological service facilities and Epistem Ltd (irradiation facilities). We also thank Stefano Rossi for his help with data analysis for the initial submission.

PY - 2024/3

Y1 - 2024/3

N2 - Background The kidney contains distinct glomerular and tubulointerstitial compartments with diverse cell types and extracellular matrix components. The role of immune cells in glomerular environment is crucial for dampening inflammation and maintaining homeostasis. Macrophages are innate immune cells that are influenced by their tissue microenvironment. However, the multifunctional role of kidney macrophages remains unclear. Methods Flow and imaging cytometry were used to determine the relative expression of CD81 and CX3CR1 (C-X3-C motif chemokine receptor 1) in kidney macrophages. Monocyte replenishment was assessed in Cx3cr1CreER X R26-yfp-reporter and shielded chimeric mice. Bulk RNA-sequencing and mass spectrometry-based proteomics were performed on isolated kidney macrophages from wild type and Col4a5−/− (Alport) mice. RNAscope was used to visualize transcripts and macrophage purity in bulk RNA assessed by CIBERSORTx analyses. Results In wild type mice we identified three distinct kidney macrophage subsets using CD81 and CX3CR1 and these subsets showed dependence on monocyte replenishment. In addition to their immune function, bulk RNA-sequencing of macrophages showed enrichment of biological processes associated with extracellular matrix. Proteomics identified collagen IV and laminins in kidney macrophages from wild type mice whilst other extracellular matrix proteins including cathepsins, ANXA2 and LAMP2 were enriched in Col4a5−/− (Alport) mice. A subset of kidney macrophages co-expressed matrix and macrophage transcripts. Conclusions We identified CD81 and CX3CR1 positive kidney macrophage subsets with distinct dependence for monocyte replenishment. Multiomic analysis demonstrated that these cells have diverse functions that underscore the importance of macrophages in kidney health and disease.

AB - Background The kidney contains distinct glomerular and tubulointerstitial compartments with diverse cell types and extracellular matrix components. The role of immune cells in glomerular environment is crucial for dampening inflammation and maintaining homeostasis. Macrophages are innate immune cells that are influenced by their tissue microenvironment. However, the multifunctional role of kidney macrophages remains unclear. Methods Flow and imaging cytometry were used to determine the relative expression of CD81 and CX3CR1 (C-X3-C motif chemokine receptor 1) in kidney macrophages. Monocyte replenishment was assessed in Cx3cr1CreER X R26-yfp-reporter and shielded chimeric mice. Bulk RNA-sequencing and mass spectrometry-based proteomics were performed on isolated kidney macrophages from wild type and Col4a5−/− (Alport) mice. RNAscope was used to visualize transcripts and macrophage purity in bulk RNA assessed by CIBERSORTx analyses. Results In wild type mice we identified three distinct kidney macrophage subsets using CD81 and CX3CR1 and these subsets showed dependence on monocyte replenishment. In addition to their immune function, bulk RNA-sequencing of macrophages showed enrichment of biological processes associated with extracellular matrix. Proteomics identified collagen IV and laminins in kidney macrophages from wild type mice whilst other extracellular matrix proteins including cathepsins, ANXA2 and LAMP2 were enriched in Col4a5−/− (Alport) mice. A subset of kidney macrophages co-expressed matrix and macrophage transcripts. Conclusions We identified CD81 and CX3CR1 positive kidney macrophage subsets with distinct dependence for monocyte replenishment. Multiomic analysis demonstrated that these cells have diverse functions that underscore the importance of macrophages in kidney health and disease.

KW - Kidney

KW - Macrophages

KW - Basement membrane

KW - Extracellular matrix

KW - Cytometry

KW - RNA-sequencing

KW - Proteomics

U2 - 10.1016/j.matbio.2024.02.002

DO - 10.1016/j.matbio.2024.02.002

M3 - Article

SN - 0945-053X

VL - 127

SP - 23

EP - 37

JO - Matrix Biology

JF - Matrix Biology

ER -

Kidney resident macrophages have distinct subsets and multifunctional roles

Abstract

Keywords / Materials (for Non-textual outputs)

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