IL-16 is differentially expressed in the developing human fetal brain by microglial cells in zones of neuropoesis

Abstract Microglial cells are regulators of tissue homeostasis in the adult central nervous system and readily participate in pathological processes, orchestrating tissue remodeling. Cytokines produced by microglial cells are markers of cell activation and contribute to reactive processes. In this paper, we have studied the expression of IL-16 (leukocyte chemoattractant factor), a natural soluble ligand to the CD4 molecule, in human fetal brains from the 11th to the 20th . week of gestation by immunohistochemistry. Interleukin (IL)-16 + cells were detected already at the 11th gestational week, accumulating with aging in cortical layers ( P + microglia (>80%) revealed morphological hallmarks of activated microglia. We observed that IL-16 cells coexpress LCA (>80%) and MRP-8, an activation-associated Ca 2+ binding S-100 family member (>80%). In contrast, only few IL-16 + cells proliferated (PCNA + , 20–40%) or co-expressed the HLA-DR, -DP, or -DQ antigen ( + microglia in zones of neuronal proliferation, migration and differentiation. Increasing numbers of IL-16 + cells were detected in bordering zones adjacent to the basal ganglia. Our data suggests that the early presence of IL-16 + microglia exert a CD4-independent function-mediating activation, and chemotaxis of microglia precursors during neuronal development. In addition, IL-16 immunoreactivity might be a helpful tool to determine distinct developmental stages of microglial cells during fetal central nervous system ontogeny.