The roles of Interleukin 34 in rat macrophage function

Interleukin 34 (IL34) and colony stimulating factor 1 (CSF1) signal through a shared receptor (CSF1R) to control macrophage survival, differentiation and function. Here we describe the impact of loss of function mutation in the rat Il34 gene. By contrast to IL34 mutant mice, macrophages within squamous epithelia (Langerhans cells) were not significantly depleted in Il34-/- rats. In the brain, microglia and brain-associated macrophages were selectively depleted in grey matter. A gradient of microglial density in Il34-/- cortex suggests that CSF1 can diffuse outwards from the corpus callosum. Microglial loss was not associated with detectable neuropathology or behavioural alterations or altered gene expression in cortex, hippocampus and thalamus aside from selective loss of microglia-expressed transcripts. In the adenine diet model of renal interstitial fibrosis both Il34 and Csf1 were induced. The absence of IL34 led to a significant reduction in macrophage recruitment compared to controls, but pathology was unaffected. We suggest that IL34 and CSF1 provide overlapping signals to sustain microglia and to direct macrophage recruitment and repair tissue injury in the periphery.