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WNT-dependent interaction between inflammatory fibroblasts and FOLR2+ macrophages promotes fibrosis in chronic kidney disease

Author

Listed:
  • Camille Cohen

    (PSL Research University
    Inserm, U830)

  • Rana Mhaidly

    (PSL Research University
    Inserm, U830)

  • Hugo Croizer

    (PSL Research University
    Inserm, U830)

  • Yann Kieffer

    (PSL Research University
    Inserm, U830)

  • Renaud Leclere

    (Institut Curie Hospital Group)

  • Anne Vincent-Salomon

    (Institut Curie Hospital Group)

  • Catherine Robley

    (PSL Research University
    Inserm, U830)

  • Dany Anglicheau

    (Paris Cité University, Inserm U1151)

  • Marion Rabant

    (Paris Cité University)

  • Aurélie Sannier

    (Paris Cité University, Inserm, U1148)

  • Marc-Olivier Timsit

    (Paris Cité University)

  • Sean Eddy

    (University of Michigan)

  • Matthias Kretzler

    (University of Michigan
    University of Michigan)

  • Wenjun Ju

    (University of Michigan
    University of Michigan)

  • Fatima Mechta-Grigoriou

    (PSL Research University
    Inserm, U830)

Abstract

Chronic kidney disease (CKD) is a public health problem driven by myofibroblast accumulation, leading to interstitial fibrosis. Heterogeneity is a recently recognized characteristic in kidney fibroblasts in CKD, but the role of different populations is still unclear. Here, we characterize a proinflammatory fibroblast population (named CXCL-iFibro), which corresponds to an early state of myofibroblast differentiation in CKD. We demonstrate that CXCL-iFibro co-localize with macrophages in the kidney and participate in their attraction, accumulation, and switch into FOLR2+ macrophages from early CKD stages on. In vitro, macrophages promote the switch of CXCL-iFibro into ECM-secreting myofibroblasts through a WNT/β-catenin-dependent pathway, thereby suggesting a reciprocal crosstalk between these populations of fibroblasts and macrophages. Finally, the detection of CXCL-iFibro at early stages of CKD is predictive of poor patient prognosis, which shows that the CXCL-iFibro population is an early player in CKD progression and demonstrates the clinical relevance of our findings.

Suggested Citation

  • Camille Cohen & Rana Mhaidly & Hugo Croizer & Yann Kieffer & Renaud Leclere & Anne Vincent-Salomon & Catherine Robley & Dany Anglicheau & Marion Rabant & Aurélie Sannier & Marc-Olivier Timsit & Sean E, 2024. "WNT-dependent interaction between inflammatory fibroblasts and FOLR2+ macrophages promotes fibrosis in chronic kidney disease," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-44886-z
    DOI: 10.1038/s41467-024-44886-z
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