杜克大学Staci D. Bilbo研究团队取得一项新突破。他们报道了兴奋性神经元来源的白介素-34支持皮层发育小胶质细胞功能。这一研究成果于2025年7月2日发表在国际顶尖学术期刊《免疫学》上。

课题组人员发现，白细胞介素-34 （IL-34）是一种神经元来源的细胞因子，在小鼠前扣带皮层（ACC）的早期发育和维持神经保护作用的成熟小胶质细胞中表达上调。IL-34的表达在出生后第二周增加，主要由兴奋性神经元产生。兴奋性神经元特异性缺失IL-34减少了ACC中小胶质细胞数量和小胶质细胞TMEM119的表达，增加了兴奋性丘脑皮质突触的异常小胶质细胞吞噬。在出生后第15天，急性低剂量阻断IL-34同样会降低小胶质细胞TMEM119，并异常增加突触的小胶质细胞吞噬。病毒过表达IL-34诱导TMEM119表达并阻止突触的适当小胶质吞噬。这些发现表明，IL-34是出生后大脑发育中神经元-小胶质细胞串音的关键调节因子，控制小胶质细胞成熟和突触吞噬。

研究人员表示，神经元与小胶质细胞的相互作用决定了大脑中神经元回路的发育。然而，在整个发展过程中调节这些过程的因素在很大程度上是未知的。

附：英文原文

Title: Excitatory-neuron-derived interleukin-34 supports cortical developmental microglia function

Author: Benjamin A. Devlin, Dang M. Nguyen, Diogo Ribeiro, Gabriel Grullon, Madeline J. Clark, Amelie Finn, Alexis M. Ceasrine, Seneca Oxendine, Martha Deja, Ashka Shah, Shomik Ati, Anne Schaefer, Staci D. Bilbo

Issue&Volume: 2025-07-02

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.

DOI: 10.1016/j.immuni.2025.06.002

Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00249-3