Key result
IL-2 complex-induced Treg expansion improves post-stroke memory and neuronal survival via astrocytic STING inhibition.
Why the study?
Excessive immune responses after ischemic stroke are associated with poor clinical prognosis, and the mechanisms by which regulatory T cells (Tregs) mediate post-stroke neurological recovery and immunotherapy remained unclear.
Does expanding regulatory T cells (Tregs) improve long-term neurological recovery and neuronal remodeling after ischemic stroke by inhibiting the astrocytic STING pathway to promote the astrocyte-neuron lactate shuttle (ANLS)?
Does expanding regulatory T cells (Tregs) improve long-term neurological recovery and neuronal remodeling after ischemic stroke by inhibiting the astrocytic STING pathway to promote the astrocyte-neuron lactate shuttle (ANLS)?
Answers are grounded in this paper and cite their sources.
This preclinical study identifies a novel mechanism whereby regulatory T cells promote post-stroke neuronal energy supply and long-term neurological recovery by inhibiting astrocytic STING signaling to enhance the astrocyte-neuron lactate shuttle.
BACKGROUND: Excessive immune response following ischemic stroke is closely associated with poor clinical prognosis. Although regulatory T cell (Treg) is recognized as pivotal immunomodulator, its potential mechanisms in post-stroke neurological recovery and immunotherapy remain unclear. METHODS: Neurological recovery and neuronal remodeling were investigated by behavior tests, HE staining, Nissl staining, and LFB staining. Monocarboxylate transporter (MCT) was detected to evaluate the role of astrocyte-neuron lactate shuttle (ANLS) in Tregs-mediated neuroprotection by immunofluorescence and western blot, lactate assay, ATP assay, and cell viability assay experiments. The expression of stimulator of interferon gene (STING) and phosphorylation of downstream factors were examined by western blot. RESULTS: Tregs significantly attenuated neuronal injury, upregulated the expression of synaptic plasticity-related proteins, promoted myelin reconstruction, and improved spatial cognition, memory function, and motor coordination. Mechanistically, Tregs enhanced MCT-mediated lactate transfer to neurons, providing energy supply for neuronal remodeling, whereas the MCT inhibitor 4-CIN reversed Tregs-mediated neuroprotection. In addition, Tregs suppressed the activation of the STING pathway, and activation of STING by DMXAA abolished the Tregs-induced potentiation of ANLS. CONCLUSIONS: This study clarifies a novel mechanism by which Tregs promote ANLS and provide energy supply for neuronal remodeling by inhibiting the STING pathway, thereby improving the long-term neurological recovery after stroke.
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Meng et al. (2026) studied Ischemic stroke (middle cerebral artery occlusion mouse model and oxygen-glucose deprivation/reoxygenation cell model). Regulatory T cell (Treg) expansion via IL-2:IL-2 antibody complex (in vivo) or Treg co-culture (in vitro) vs. IgG isotype control or vehicle; co-administration of MCT inhibitor 4-CIN (100 mg/kg) or STING agonist DMXAA (15 mg/kg) was evaluated on Long-term neurological recovery (spatial cognitive/memory function via Morris water maze and motor coordination via rotarod test), neuronal remodeling, and astrocyte-neuron lactate shuttle (ANLS) activity via MCT4/MCT2 and STING pathway expression (p=<0.0001). Treg expansion via IL-2:IL-2 antibody complex improved post-stroke spatial memory and neuronal survival by inhibiting astrocytic STING to promote MCT-mediated lactate shuttle.
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