NKT cells promote both type 1 and type 2 inflammatory responses in a mouse model of liver fibrosis

Julia Nilsson, Maria Hörnberg, Anja Schmidt-Christensen, Kajsa Linde, Maria Nilsson, Marine Carlus, Saskia F. Erttmann, Sofia Mayans, Dan Holmberg

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

Sammanfattning

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.

Originalspråkengelska
Artikelnummer21778
TidskriftScientific Reports
Volym10
Nummer1
DOI
StatusPublished - 2020

Ämnesklassifikation (UKÄ)

  • Immunologi inom det medicinska området

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