|
| Status |
Public on Feb 19, 2024 |
| Title |
Lipocalin-2 expression identifies an immuno-regulatory intestinal neutrophil population during GVHD |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Acute graft-versus-host disease (aGVHD) is a life-threatening complication of allogeneic hematopoietic cell transplantation (allo-HCT). 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, while the lack of epithelial or hematopoietic LCN2 enhanced aGVHD severity and caused microbiome alterations. Mechanistically, LCN2 induced IGF-1R signaling in macrophages via the LCN2 receptor Slc22A17, which increased IL-10 production while reducing MHC-II expression. Transfer of LCN2-pretreated macrophages reduced aGVHD severity. LCN2-treatment did not reduce graft-versus-leukemia effects. In aGVHD patients LCN2 expression correlated with IL-10 expression in intestinal biopsies. We identified a novel intestinal LCN2+ neutrophil population that reduces aGVHD-severity by decreasing MHC-II expression while increasing IL-10 production in macrophages. Administration of LCN2 presents a novel approach against aGVHD to be tested in clinical trials.
|
| |
|
| Overall design |
Single-cell RNA sequencing was performed on neutrophils (CD45+H2kb+CD11b+Ly6G+) residing in the terminal ileum on day 21 after allogeneic hematopoietic cell transplantation. BALB/c mice receiving 5 x 10ˆ6 BM cells with 4 x 10ˆ5 T cells from C57BL/6 donor mice developed acute GVHD, while BALB/c mice receiving only 5 x 10ˆ6 BM cells from C57BL/6 serve as a control.
|
| |
|
| Contributor(s) |
Peltokangas N, Grün D, Hülsdünker J, Zeiser R |
| Citation(s) |
38381845 |
| |
| Submission date |
Mar 09, 2023 |
| Last update date |
Jun 17, 2024 |
| Contact name |
Nina Peltokangas |
| E-mail(s) |
peltokangas@ie-freiburg.mpg.de
|
| Organization name |
Max Planck Institute of Immunobiology and Epigenetics
|
| Street address |
Stübeweg 51
|
| City |
Freiburg |
| ZIP/Postal code |
79108 |
| Country |
Germany |
| |
|
| Platforms (1) |
| GPL21493 |
Illumina HiSeq 3000 (Mus musculus) |
|
| Samples (22)
|
|
| Relations |
| BioProject |
PRJNA943060 |
Less...
More...