| First Author | Gonzatti MB | Year | 2023 |
| Journal | iScience | Volume | 26 |
| Issue | 10 | Pages | 107947 |
| PubMed ID | 37841583 | Mgi Jnum | J:341722 |
| Mgi Id | MGI:7542555 | Doi | 10.1016/j.isci.2023.107947 |
| Citation | Gonzatti MB, et al. (2023) Targeting adrenergic receptors to mitigate invariant natural killer T cells-induced acute liver injury. iScience 26(10):107947 |
| abstractText | Invariant Natural Killer T (iNKT) cell activation by alpha-galactosylceramide (alphaGC) potentiates cytotoxic immune responses against tumors. However, alphaGC-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 alphaGC-induced liver injury without impairing iNKT cells' antitumoral functions. Mechanistically, SNS stimulation prevents the collateral effect of TNF-alpha 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 alphaGC-based immunotherapy to mitigate iNKT-induced liver injury without compromising its antitumoral activity. |
