Cell Reports (Jun 2024)
Protective role for kidney TREM2high macrophages in obesity- and diabetes-induced kidney injury
- Ayshwarya Subramanian,
- Katherine A. Vernon,
- Yiming Zhou,
- Jamie L. Marshall,
- Maria Alimova,
- Carlos Arevalo,
- Fan Zhang,
- Michal Slyper,
- Julia Waldman,
- Monica S. Montesinos,
- Danielle Dionne,
- Lan T. Nguyen,
- Michael S. Cuoco,
- Dan Dubinsky,
- Jason Purnell,
- Keith Keller,
- Samuel H. Sturner,
- Elizabeth Grinkevich,
- Ayan Ghoshal,
- Amanda Kotek,
- Giorgio Trivioli,
- Nathan Richoz,
- Mary B. Humphrey,
- Isabella G. Darby,
- Sarah J. Miller,
- Yingping Xu,
- Astrid Weins,
- Alexandra Chloe-Villani,
- Steven L. Chang,
- Matthias Kretzler,
- Orit Rosenblatt-Rosen,
- Jillian L. Shaw,
- Kurt A. Zimmerman,
- Menna R. Clatworthy,
- Aviv Regev,
- Anna Greka
Affiliations
- Ayshwarya Subramanian
- Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Corresponding author
- Katherine A. Vernon
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Yiming Zhou
- Broad Institute of MIT and Harvard, Cambridge, MA, USA; Corresponding author
- Jamie L. Marshall
- Broad Institute of MIT and Harvard, Cambridge, MA, USA; Kidney Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Maria Alimova
- Kidney Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Carlos Arevalo
- Broad Institute of MIT and Harvard, Cambridge, MA, USA; Kidney Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Fan Zhang
- Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
- Michal Slyper
- Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Julia Waldman
- Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Monica S. Montesinos
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Danielle Dionne
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Lan T. Nguyen
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Michael S. Cuoco
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Dan Dubinsky
- Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Jason Purnell
- Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Keith Keller
- Kidney Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Samuel H. Sturner
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Elizabeth Grinkevich
- Kidney Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Ayan Ghoshal
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Amanda Kotek
- Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
- Giorgio Trivioli
- Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, UK; Nephrology Department, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
- Nathan Richoz
- Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, UK
- Mary B. Humphrey
- Department of Internal Medicine, Division of Nephrology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Isabella G. Darby
- Department of Internal Medicine, Division of Nephrology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Sarah J. Miller
- Department of Internal Medicine, Division of Nephrology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Yingping Xu
- Institute of Dermatology and Venereology, Dermatology Hospital, Southern Medical University, Guangzhou, China
- Astrid Weins
- Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA; Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
- Alexandra Chloe-Villani
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Steven L. Chang
- Center for Surgery and Public Health, Brigham and Women’s Hospital, Boston, MA, USA; Division of Urology, Brigham and Women’s Hospital, Boston, MA, USA
- Matthias Kretzler
- Internal Medicine, Department of Nephrology, University of Michigan, Ann Arbor, MI, USA
- Orit Rosenblatt-Rosen
- Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Jillian L. Shaw
- Broad Institute of MIT and Harvard, Cambridge, MA, USA; Kidney Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Kurt A. Zimmerman
- Department of Internal Medicine, Division of Nephrology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Menna R. Clatworthy
- Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, UK; Cellular Genetics, Wellcome Sanger Institute, Hinxton, UK; NIHR Cambridge Biomedical Research Center, Cambridge, UK; Cambridge Institute of Therapeutic Immunology and Infectious Diseases, Cambridge, UK
- Aviv Regev
- Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA
- Anna Greka
- Broad Institute of MIT and Harvard, Cambridge, MA, USA; Kidney Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA; Corresponding author
- Journal volume & issue
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Vol. 43,
no. 6
p. 114253
Abstract
Summary: Diabetic kidney disease (DKD), the most common cause of kidney failure, is a frequent complication of diabetes and obesity, and yet to date, treatments to halt its progression are lacking. We analyze kidney single-cell transcriptomic profiles from DKD patients and two DKD mouse models at multiple time points along disease progression—high-fat diet (HFD)-fed mice aged to 90–100 weeks and BTBR ob/ob mice (a genetic model)—and report an expanding population of macrophages with high expression of triggering receptor expressed on myeloid cells 2 (TREM2) in HFD-fed mice. TREM2high macrophages are enriched in obese and diabetic patients, in contrast to hypertensive patients or healthy controls in an independent validation cohort. Trem2 knockout mice on an HFD have worsening kidney filter damage and increased tubular epithelial cell injury, all signs of worsening DKD. Together, our studies suggest that strategies to enhance kidney TREM2high macrophages may provide therapeutic benefits for DKD.
