Abstract：
: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.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Nilsson J,Hörnberg M,Schmidt-Christensen A,Linde K,Nilsson M,Carlus M,Erttmann SF,Mayans S,Holmberg Ddoi
10.1038/s41598-020-78688-2subject
Has Abstractpub_date
2020-12-11 00:00:00pages
21778issue
1issn
2045-2322pii
10.1038/s41598-020-78688-2journal_volume
10pub_type
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