The mononuclear phagocyte system contributes to fibrosis in post-transplant obliterans bronchiolitis.

Bronchiolitis obliterans syndrome (BOS) is a fibrotic disease that is heavily responsible for the high mortality rates after lung transplantation. Myofibroblasts are primary effectors of this fibrotic process, but their origin is still debated. The purpose of this work was to identify the precursors of mesenchymal cells responsible for post-transplant airway fibro-obliteration.Lineage-tracing tools were used to track or deplete potential sources of myofibroblasts in the heterotopic tracheal transplantation model. Allografts were analysed by histology, confocal microscopy, flow cytometry or single-cell transcriptomic analysis. BOS explants were evaluated by histology and confocal microscopy.Myofibroblasts in the allografts were recipient-derived. When recipient mice were treated with tacrolimus, we observed rare epithelial-to-mesenchymal transition phenomena and an overall increase in donor-derived myofibroblasts (p=0.0467), but the proportion of these cells remained low (7%). Haematopoietic cells, and specifically the mononuclear phagocyte system, gave rise to the majority of myofibroblasts found in occluded airways. Ablation of Cx3cR1

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Déclaration de conflit d'intérêts

Conflict of interest: M-P. Di Campli has nothing to disclose. Conflict of interest: A. Azouz has nothing to disclose. Conflict of interest: A. Assabban has nothing to disclose. Conflict of interest: J. Scaillet has nothing to disclose. Conflict of interest: M. Splittgerber has nothing to disclose. Conflict of interest: A. Van Keymeulen has nothing to disclose. Conflict of interest: F. Libert has nothing to disclose. Conflict of interest: M. Remmelink has nothing to disclose. Conflict of interest: A. Le Moine has nothing to disclose. Conflict of interest: P. Lemaitre has nothing to disclose. Conflict of interest: S. Goriely has nothing to disclose.