Targeting adrenergic receptors to mitigate iNKT-induced acute liver injury

Michelangelo Bauwelz Gonzatti, Beatriz Marton Freire,Maísa Mota Antunes, Gustavo B. Menezes, Jhimmy Talbot, Jean Pierre Schatzmann Peron,Alexandre Salgado Basso,Alexandre C. Keller

iScience(2023)

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摘要
Invariant Natural Killer T (iNKT) cell activation by α-galactosylceramide (αGC) potentiates cytotoxic immune responses against tumors. However, αGC-induced liver injury is a limiting factor for iNKT-based immunotherapy. Although adrenergic receptor stimulation is an important immunosuppressive signal that curbs tissue damage induced by inflammation, its effect on the antitumor activity of invariant Natural Killer T (iNKT) cells remains unclear. We use mouse models and pharmacological tools to show that the stimulation of the sympathetic nervous system (SNS) inhibits αGC-induced liver injury without impairing iNKT cells' antitumoral functions. Mechanistically, SNS stimulation prevents the collateral effect of TNF-α production by iNKT cells and neutrophil accumulation in hepatic parenchyma. Our results suggest that the modulation of the adrenergic signaling can be a complementary approach to αGC-based immunotherapy to mitigate iNKT-induced liver injury without compromising its antitumoral activity.
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关键词
acute liver injury,adrenergic receptors,inkt-induced
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