| Autor: |
Nilsson J; Department of Experimental Medical Sciences, Lund University Diabetes Center, Clinical Research Center, Lund University, Jan Waldenströms gata 35, 214 28, Malmö, Sweden.; InfiCure Bio AB, Tvistevägen 48 C, 907 36, Umeå, Sweden., Hörnberg M; InfiCure Bio AB, Tvistevägen 48 C, 907 36, Umeå, Sweden., Schmidt-Christensen A; Department of Experimental Medical Sciences, Lund University Diabetes Center, Clinical Research Center, Lund University, Jan Waldenströms gata 35, 214 28, Malmö, Sweden., Linde K; InfiCure Bio AB, Tvistevägen 48 C, 907 36, Umeå, Sweden., Nilsson M; Department of Experimental Medical Sciences, Lund University Diabetes Center, Clinical Research Center, Lund University, Jan Waldenströms gata 35, 214 28, Malmö, Sweden., Carlus M; Carlus Pathology Consulting, 2 rue de la Libération, 76630, Bellengreville, France., Erttmann SF; Department of Molecular Biology, Umeå University, 901 87, Umeå, Sweden., Mayans S; InfiCure Bio AB, Tvistevägen 48 C, 907 36, Umeå, Sweden., Holmberg D; Department of Experimental Medical Sciences, Lund University Diabetes Center, Clinical Research Center, Lund University, Jan Waldenströms gata 35, 214 28, Malmö, Sweden. dan.holmberg@med.lu.se.; InfiCure Bio AB, Tvistevägen 48 C, 907 36, Umeå, Sweden. dan.holmberg@med.lu.se. |
| Abstrakt: |
Sterile liver inflammation and fibrosis are associated with many liver disorders of different etiologies. Both type 1 and type 2 inflammatory responses have been reported to contribute to liver pathology. However, the mechanisms controlling the balance between these responses are largely unknown. Natural killer T (NKT) cells can be activated to rapidly secrete cytokines and chemokines associated with both type 1 and type 2 inflammatory responses. As these proteins have been reported to accumulate in different types of sterile liver inflammation, we hypothesized that these cells may play a role in this pathological process. We have found that a transgenic NKT (tgNKT) cell population produced in the immunodeficient 2,4αβNOD.Rag2 -/- mice, but not in 2,4αβNOD.Rag2 +/- control mice, promoted a type 1 inflammatory response with engagement of the NOD-, LRR- and pyrin domain-containing protein-3 (NLRP3) inflammasome. The induction of the type 1 inflammatory response was followed by an altered cytokine profile of the tgNKT cell population with a biased production of anti-inflammatory/profibrotic cytokines and development of liver fibrosis. These findings illustrate how the plasticity of NKT cells modulates the inflammatory response, suggesting a key role for the NKT cell population in the control of sterile liver inflammation. |
