Macrophage polarization, inflammatory monocytes, and impaired MDSCs are associated with murine and human immune aplastic anemia.

ABSTRACT: Immune-mediated bone marrow failure (BMF) entails a complex immune landscape. Myeloid cells, including monocytes, macrophages, and myeloid-derived suppressor cells (MDSCs), are involved in the development and progression of immune aplastic anemia (AA). We used a murine model of BMF to explore the effects of CSF-1R inhibition on immune pathophysiology. Hematopoiesis, immune cell populations, and gene expression were assessed by flow cytometry, cytokine analysis, and single-cell RNA sequencing. CSF-1R inhibition with the small molecule PLX3397 intensified BMF in CByB6F1 mice, enhancing inflammation and macrophage polarization toward the proinflammatory M1 phenotype. This was accompanied by increased leukocyte apoptosis, a reduction in CD11b + myeloid cells, and worsened animal survival. In c

SUBMITTER: Glass J 

PROVIDER: S-EPMC12202376 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature