WNT-dependent interaction between inflammatory fibroblasts and FOLR2+ macrophages promotes fibrosis in chronic kidney disease
Year: 2024
Type: article
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.
Source: Nature Communications
Institutions: Inserm, Université Paris Sciences et Lettres, La Ligue Contre le Cancer, Institut Curie, Hôpital Necker-Enfants Malades, Université Paris Cité, Assistance Publique – Hôpitaux de Paris, Laboratoire de Recherche Vasculaire Translationnelle, Hôpital Bichat-Claude-Bernard, Hôpital Européen Georges-Pompidou, University of Michigan
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,790
Funders: Nephcure Foundation, NHS Blood and Transplant, Fondation Simone et Cino Del Duca, Rare Diseases Clinical Research Network, Institut National de la Santé et de la Recherche Médicale, Fondation pour la Recherche Médicale, Institut National Du Cancer, Direction Générale de l’offre de Soins, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Advancing Translational Sciences
Awards: University of Michigan O'Brien Kidney Translational Core Center, Cancer and lymphoid stroma (CALYS): deciphering stromal heterogeneity – identity, origins and functions – in solid and lymphoid cancers, Deciphering the impact of STROMA in high grade serous Epithelial Ovarian Carcinomas, ChemoCAFs : Chemotherapeutic response of fibroblast ecosystems in human breast cancer at single cell resolution, Spatial and molecular characterization of stromal heterogeneity and plasticity in cancer, Nephrotic Syndrome Rare Disease Clinical Research Network III
OpenAlex ID: W4391230697