Microglial Transmembrane 119 (Tmem119) is Protective in Ischemic Stroke
Year: 2026
Type: article
Abstract: Microglial responses to cerebral ischemia are tightly regulated by inhibitory pathways that limit excessive post-stroke inflammation. Transmembrane protein 119 (Tmem119) has emerged as an important regulator of microglial activation and neuroinflammatory signaling. We investigated the role of microglial Tmem119 during acute ischemic stroke using primary microglia and a young adult mouse model. Primary microglia were transfected with Tmem119-siRNA and subjected to oxygen-glucose deprivation (OGD) alone or combined with lipopolysaccharide (LPS) stimulation. In vivo, young adult male mice received stereotaxic injection of lenti-Tmem119 or lenti-GFP for 4 weeks before 60 min of transient middle cerebral artery occlusion (MCAO). Tmem119 expression and inflammatory responses were assessed by qPCR, Western blotting, and ELISA at 1 and 3 days after stroke. Infarct volume and neurobehavioral outcomes were also evaluated. Tmem119 silencing significantly increased IRAK4, IRF5, and CD68 mRNA expression in primary microglia. Ischemic injury reduced microglial Tmem119 protein expression and increased IRAK4 signaling in vivo. In contrast, lenti-Tmem119 treatment before MCAO decreased phosphorylated IRAK4 protein expression and increased IL-10 levels in both plasma and ischemic brain tissue compared with lenti-GFP controls. Tmem119 overexpression also significantly reduced infarct volume and improved neurobehavioral outcomes. These findings demonstrate that microglial Tmem119 exerts a protective anti-inflammatory role during the acute phase of ischemic stroke by suppressing IRAK4-mediated inflammatory signaling and enhancing IL-10 production. Collectively, Tmem119 limits microglial activation, reduces ischemic brain injury, and improves functional recovery, identifying Tmem119 as a promising therapeutic target for ischemic stroke.
Source: Glia
DOI: 10.1002/glia.70249
Language: English
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $5,450
OpenAlex ID: W7225622205