A Subset of Pro-inflammatory CXCL10+ LILRB2+ Macrophages Derives From Recipient Monocytes and Drives Renal Allograft Rejection.

Fiche publication

Date publication

janvier 2026

Journal

Advanced science (Weinheim, Baden-Wurttemberg, Germany)

Auteurs

Membres identifiés du Cancéropôle Est :
Pr DUCLOUX Didier , Pr MARTIN Laurent , Dr RENOSI Florian , Dr ROUSSEL Xavier

Tous les auteurs :
Varin A, Palvair J, Messager L, Bamoulid J, Callemeyn J, Chaintreuil M, Zuffo LD, Ducloux D, Farhat I, Legendre M, Martin L, Renosi F, Roussel X, Vaulet T, Naesens M, Tinel C, Lamarthée B

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/41517835

Résumé

In solid organ transplantation, monocytes and macrophages play a cross-cutting role in the rejection process, irrespective of the transplanted tissue and the type of rejection. Here, we integrated multiple single-cell assays (>150,000 cells) with a broad spectrum of blood-derived and renal allograft-derived cells. We observed 6 myeloid cell trajectories enriched in the allograft during rejection, ranging from circulating CD14+ monocytes to differentiated macrophages in the kidney, with one trajectory culminating in a pro-inflammatory macrophage expressing CXCL9 and CXCL10. By analyzing over 850 biopsies using deconvolution, we report that they are absent in pre-transplant allografts, while these CXCL10+ macrophages are the immune cells most associated with inflammation during acute rejection. Furthermore, a survival study of over 500 biopsies indicates that they increase the risk of graft loss independently of other immune cells. CXCL10+ macrophages differentiate from recipient monocytes, and we have identified 6 major genes associated with their differentiation, including LILRB2. In vitro, mimicking allogenic activation of blood monocytes via the CD47/SIRP-a axis induced overexpression of LILRB2, suggesting that CXCL10+ macrophages are activated by this pathway. Finally, we show that macrophages overexpressing LILRB2 induce the proliferation of autologous T lymphocytes. Altogether, the present study provides further insight into the pro-inflammatory axes of recipient-derived monocytes/macrophages, and suggests LILRB2 as a therapeutic target.