CSF1R inhibition by a small molecule inhibitor affects hematopoiesis and the function of macrophages.

Abstract

Colony-stimulating factor 1 receptor (CSF1R) inhibition has been proposed as a method for microglia depletion, with the assumption that it does not affect peripheral immune cells. Here, we show that CSF1R inhibition by PLX5622 indeed affects the myeloid and lymphoid compartments, causes long-term changes in bone marrow-derived macrophages by suppressing their IL-1{beta}, CD68 and phagocytosis, but not CD208, following exposure to endotoxin, and also reduces the population of tissue resident macrophages of peritoneum, lung, liver, but not spleen. Thus, small molecule CSF1R inhibition is not restricted to microglia only, but rather causes strong effects on circulating and tissue macrophages that perdure long after cessation of the treatment. Given that peripheral monocytes repopulate the CNS after CSF1R inhibition, these changes may have practical implications on relevant experimental data.