GM-CSF receptor expression determines opposing innate memory phenotypes at different stages of myelopoiesis.

ABSTRACT:

Abstract

Inflammatory responses must be tightly coordinated with the activation of emergency myelopoiesis to produce potent myeloid cells that fight infection without causing excessive host damage. Here, we show that granulocyte-macrophage colony-stimulating factor (GM-CSF) programs myeloid-committed progenitors to produce trained macrophages (increased cytokine response), but programs the upstream noncommitted LKS+ progenitors (defined as Lin- c-Kit+ Sca-1+ cells) to produce tolerized macrophages (decreased cytokine response). In myeloid progenitors, GM-CSF strongly activates signal transducer and activator of transcription 5 (STAT5), Ras-Raf-extracellular signal regulated kinase (ERK), and Akt-mTOR signaling pathways, which are essential to establish a training program, whereas i

SUBMITTER: Guerrero P 

PROVIDER: S-EPMC11251219 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature