Huang Stephen, Patkar Omkar L, Schulze Sarah, Carter-Cusack Dylan, Millard Susan, Ranpura Ginell, Green Emma K, Maxwell Emma, Kanesarajah Jeeva, Cowin Gary, Stimson Damion, Kurniawan Nyoman D, Keshvari Sahar, Allavena Rachel, Pettit Allison R, Irvine Katharine M, Hume David A
Mater Research Institute-UQ, Translational Research Institute, Brisbane, Australia.
QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Life Sci Alliance. 2025 Jun 18;8(9). doi: 10.26508/lsa.202503264. Print 2025 Sep.
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 gene. In contrast to IL34 mutant mice, macrophages within squamous epithelia (Langerhans cells) were not significantly depleted in rats. In the brain, microglia and brain-associated macrophages were selectively depleted in grey matter. A gradient of microglial density in the cortex suggests that CSF1 can diffuse outwards from the corpus callosum. Microglial loss was not associated with detectable neuropathology or altered gene expression in the cortex, hippocampus, and thalamus aside from selective loss of microglia-expressed transcripts. In the adenine diet model of renal interstitial fibrosis, both and were induced. The absence of IL34 led to a significant reduction in macrophage recruitment compared with 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.
白细胞介素34（IL34）和集落刺激因子1（CSF1）通过共同受体（CSF1R）发出信号，以控制巨噬细胞的存活、分化和功能。在此，我们描述了大鼠基因功能丧失突变的影响。与IL34突变小鼠不同，鳞状上皮内的巨噬细胞（朗格汉斯细胞）在大鼠中并未显著减少。在大脑中，小胶质细胞和脑相关巨噬细胞在灰质中被选择性耗尽。皮质中小胶质细胞密度的梯度表明CSF1可以从胼胝体向外扩散。除了小胶质细胞表达的转录本选择性丢失外，小胶质细胞的丢失与皮质、海马体和丘脑中可检测到的神经病理学或基因表达改变无关。在肾间质纤维化的腺嘌呤饮食模型中，IL34和CSF1均被诱导。与对照组相比，IL34的缺失导致巨噬细胞募集显著减少，但病理学未受影响。我们认为，IL34和CSF1提供重叠信号以维持小胶质细胞，并在外周引导巨噬细胞募集和修复组织损伤。
