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

Nilsson, Julia LU ; Hörnberg, Maria ; Schmidt-Christensen, Anja LU orcid ; Linde, Kajsa ; Nilsson, Maria ; Carlus, Marine ; Erttmann, Saskia F. ; Mayans, Sofia and Holmberg, Dan LU (2020) In Scientific Reports 10(1).
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
10
issue
1
article number
21778
publisher
Nature Publishing Group
external identifiers
  • scopus:85097369222
  • pmid:33311540
ISSN
2045-2322
DOI
10.1038/s41598-020-78688-2
language
English
LU publication?
yes
id
4e791e26-2bf2-4f30-adfc-c49b44b0d7dd
date added to LUP
2020-12-22 07:33:28
date last changed
2025-01-11 00:57:21
@article{4e791e26-2bf2-4f30-adfc-c49b44b0d7dd,
  abstract     = {{<p>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<sup>−/−</sup> mice, but not in 2,4αβNOD.Rag2<sup>+/−</sup> 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.</p>}},
  author       = {{Nilsson, Julia and Hörnberg, Maria and Schmidt-Christensen, Anja and Linde, Kajsa and Nilsson, Maria and Carlus, Marine and Erttmann, Saskia F. and Mayans, Sofia and Holmberg, Dan}},
  issn         = {{2045-2322}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{NKT cells promote both type 1 and type 2 inflammatory responses in a mouse model of liver fibrosis}},
  url          = {{http://dx.doi.org/10.1038/s41598-020-78688-2}},
  doi          = {{10.1038/s41598-020-78688-2}},
  volume       = {{10}},
  year         = {{2020}},
}