Group 2 innate lymphoid cells resolve neuroinflammation following cerebral ischaemia.

BACKGROUND: Acute brain ischaemia elicits pronounced inflammation, which aggravates neural injury. However, the mechanisms governing the resolution of acute neuroinflammation remain poorly understood. In contrast to regulatory T and B cells, group 2 innate lymphoid cells (ILC2s) are immunoregulatory cells that can be swiftly mobilised without antigen presentation; whether and how these ILC2s participate in central nervous system inflammation following brain ischaemia is still unknown. METHODS: Leveraging brain tissues from patients who had an ischaemic stroke and a mouse model of focal ischaemia, we characterised the presence and cytokine release of brain-infiltrating ILC2s. The impact of ILC2s on neural injury was evaluated through antibody depletion and ILC2 adoptive transfer experiments. Using Rag2-/-γc-/- mice receiving passive transfer of IL-4-/- ILC2s, we further assessed the contribution of interleukin (IL)-4, produced by ILC2s, in ischaemic brain injury. RESULTS: We demonstrate that ILC2s accumulate in the areas surrounding the infarct in brain tissues of patients with cerebral ischaemia, as well as in mice subjected to focal cerebral ischaemia. Oligodendrocytes were a major source of IL-33, which contributed to ILC2s mobilisation. Adoptive transfer and expansion of ILC2s reduced brain infarction. Importantly, brain-infiltrating ILC2s reduced the magnitude of stroke injury severity through the production of IL-4. CONCLUSIONS: Our findings revealed that brain ischaemia mobilises ILC2s to curb neuroinflammation and brain injury, expanding the current understanding of inflammatory networks following stroke.

Pertussis toxin-induced inflammatory response exacerbates intracerebral haemorrhage and ischaemic stroke in mice.

BACKGROUND: Stroke is a devastating disease, including intracerebral haemorrhage (ICH) and ischaemic stroke. Emerging evidences indicate that systemic inflammatory cascades after stroke contribute to brain damage. However, the direct effects and features of systemic inflammation on brain injury, especially comparing between ischaemic and haemorrhagic stroke, are still obscure. METHODS: Pertussis toxin (PT) was used to build a pro-inflammatory milieu after ICH and ischaemic stroke in mouse model. The neurodeficits, stroke lesion, immune response and blood-brain barrier (BBB) destruction were assessed. RESULTS: In ICH mouse model, PT-induced systemic inflammation exacerbated neurological deficits, and enlarged haemorrhage lesion and perihaematomal oedema. We also found promoted leucocyte infiltration and inflammatory cytokine release into the brain after PT treatment. Moreover, the integrity of the BBB was further disrupted after receiving PT. Furthermore, we demonstrated that PT enhanced brain inflammation and aggravated stroke severity in middle cerebral artery occlusion mouse model. CONCLUSIONS: Our results suggest that PT increases inflammatory response that exacerbates brain injury after ICH or ischaemic stroke in mouse model.