Czech, Marie and Schneider, Sophia and Peltokangas, Nina and El Khawanky, Nadia and Ghimire, Sakhila and Andrieux, Geoffroy and Huelsduenker, Jan and Krausz, Mate and Proietti, Michele and Braun, Lukas M. and Rueckert, Tamina and Langenbach, Marlene and Schmidt, Dominik and Martin, Ina and Wenger, Valentin and de Vega, Enrique and Haring, Eileen and Pourjam, Mohsen and Pfeifer, Dietmar and Schmitt-Graeff, Annette and Grimbacher, Bodo and Aumann, Konrad and Kircher, Brigitte and Tilg, Herbert and Raffatellu, Manuela and Orberg, Erik Thiele and Haecker, Georg and Duyster, Justus and Koehler, Natalie and Holler, Ernst and Nachbaur, David and Boerries, Melanie and Gerner, Romana R. and Gruen, Dominic and Zeiser, Robert (2024) Lipocalin-2 expression identifies an intestinal regulatory neutrophil population during acute graft-versus-host disease. SCIENCE TRANSLATIONAL MEDICINE, 16 (735): eadi1501. ISSN 1946-6234, 1946-6242
Full text not available from this repository. (Request a copy)Abstract
Acute graft-versus-host disease (aGVHD) is a life-threatening complication of allogeneic hematopoietic cell transplantation (allo-HCT), for which therapeutic options are limited. Strategies to promote intestinal tissue tolerance during aGVHD may improve patient outcomes. Using single-cell RNA sequencing, we identified a lipocalin-2 (LCN2)-expressing neutrophil population in mice with intestinal aGVHD. Transfer of LCN2-overexpressing neutrophils or treatment with recombinant LCN2 reduced aGVHD severity, whereas the lack of epithelial or hematopoietic LCN2 enhanced aGVHD severity and caused microbiome alterations. Mechanistically, LCN2 induced insulin-like growth factor 1 receptor (IGF-1R) signaling in macrophages through the LCN2 receptor SLC22A17, which increased interleukin-10 (IL-10) production and reduced major histocompatibility complex class II (MHCII) expression. Transfer of LCN2-pretreated macrophages reduced aGVHD severity but did not reduce graft-versus-leukemia effects. Furthermore, LCN2 expression correlated with IL-10 expression in intestinal biopsies in multiple cohorts of patients with aGVHD, and LCN2 induced IGF-1R signaling in human macrophages. Collectively, we identified a LCN2-expressing intestinal neutrophil population that reduced aGVHD severity by decreasing MHCII expression and increasing IL-10 production in macrophages. This work provides the foundation for administration of LCN2 as a therapeutic approach for aGVHD.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GELATINASE-ASSOCIATED LIPOCALIN; INNATE LYMPHOID-CELLS; STEM-CELL; IN-VIVO; TRANSPLANTATION; INFLAMMATION; ACTIVATION; PROTECTS; PATHWAY; DAMAGE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Aug 2025 06:07 |
| Last Modified: | 14 Aug 2025 06:07 |
| URI: | https://pred.uni-regensburg.de/id/eprint/65654 |
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