|
| Publications [#383899] of Staci D. Bilbo
search PubMed.Journal Articles
- Devlin, BA; Nguyen, DM; Ribeiro, D; Grullon, G; Clark, MJ; Finn, A; Ceasrine, AM; Oxendine, S; Deja, M; Shah, A; Ati, S; Schaefer, A; Bilbo, SD (2025). Excitatory-neuron-derived interleukin-34 supports cortical developmental microglia function.. Immunity, 58(8), 1948-1965.e6. [doi]
(last updated on 2026/01/18)
Abstract: Neuron-microglia interactions dictate the development of neuronal circuits in the brain. However, the factors that regulate these processes across development are largely unknown. Here, we found that interleukin-34 (IL-34), a neuron-derived cytokine, was upregulated in early development and maintained neuroprotective, mature microglia in the anterior cingulate cortex (ACC) of mice. IL-34 expression increases in the second week of post-natal life and was primarily produced by excitatory neurons. Excitatory-neuron-specific deletion of IL-34 reduced microglia numbers and microglial TMEM119 expression and increased aberrant microglial phagocytosis of excitatory thalamocortical synapses in the ACC. Acute, low-dose blocking of IL-34 at post-natal day 15 similarly decreased microglial TMEM119 and aberrantly increased microglial phagocytosis of synapses. Viral overexpression of IL-34 induced TMEM119 expression and prevented appropriate microglial phagocytosis of synapses. These findings establish IL-34 as a key regulator of neuron-microglia crosstalk in post-natal brain development, controlling both microglial maturation and synapse engulfment.
|