Brain Ischemia Suppresses Immunity in the Periphery and Brain via Different Neurogenic Innervations

Qiang Liu, Wei Na Jin, Yaou Liu, Kaibin Shi, Haoran Sun, Fang Zhang, Chao Zhang, Rayna J Gonzales, Kevin N. Sheth, Antonio La Cava, Fu Dong Shi

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Brain ischemia inhibits immune function systemically, with resulting infectious complications. Whether in stroke different immune alterations occur in brain and periphery and whether analogous mechanisms operate in these compartments remains unclear. Here we show that in patients with ischemic stroke and in mice subjected to middle cerebral artery occlusion, natural killer (NK) cells display remarkably distinct temporal and transcriptome profiles in the brain as compared to the periphery. The activation of catecholaminergic and hypothalamic-pituitary-adrenal axis leads to splenic atrophy and contraction of NK cell numbers in the periphery through a modulated expression of SOCS3, whereas cholinergic innervation-mediated suppression of NK cell responses in the brain involves RUNX3. Importantly, pharmacological or genetic ablation of innervation preserved NK cell function and restrained post-stroke infection. Thus, brain ischemia compromises NK cell-mediated immune defenses through mechanisms that differ in the brain versus the periphery, and targeted inhibition of neurogenic innervation limits post-stroke infection.

Original languageEnglish (US)
Pages (from-to)474-487
Number of pages14
JournalImmunity
Volume46
Issue number3
DOIs
StatePublished - Mar 21 2017

Keywords

  • brain ischemia
  • immunity
  • natural killer (NK) cells
  • neurogenic innervation
  • post-stroke infection

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Liu, Q., Jin, W. N., Liu, Y., Shi, K., Sun, H., Zhang, F., Zhang, C., Gonzales, R. J., Sheth, K. N., La Cava, A., & Shi, F. D. (2017). Brain Ischemia Suppresses Immunity in the Periphery and Brain via Different Neurogenic Innervations. Immunity, 46(3), 474-487. https://doi.org/10.1016/j.immuni.2017.02.015