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

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 un...

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Autores principales:	Julia Nilsson, Maria Hörnberg, Anja Schmidt-Christensen, Kajsa Linde, Maria Nilsson, Marine Carlus, Saskia F. Erttmann, Sofia Mayans, Dan Holmberg
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bddd626351e343c4987a764b323cded1
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spelling	oai:doaj.org-article:bddd626351e343c4987a764b323cded12021-12-02T16:18:05ZNKT cells promote both type 1 and type 2 inflammatory responses in a mouse model of liver fibrosis10.1038/s41598-020-78688-22045-2322https://doaj.org/article/bddd626351e343c4987a764b323cded12020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78688-2https://doaj.org/toc/2045-2322Abstract 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.Julia NilssonMaria HörnbergAnja Schmidt-ChristensenKajsa LindeMaria NilssonMarine CarlusSaskia F. ErttmannSofia MayansDan HolmbergNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-15 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Julia Nilsson Maria Hörnberg Anja Schmidt-Christensen Kajsa Linde Maria Nilsson Marine Carlus Saskia F. Erttmann Sofia Mayans Dan Holmberg NKT cells promote both type 1 and type 2 inflammatory responses in a mouse model of liver fibrosis
description	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.
format	article
author	Julia Nilsson Maria Hörnberg Anja Schmidt-Christensen Kajsa Linde Maria Nilsson Marine Carlus Saskia F. Erttmann Sofia Mayans Dan Holmberg
author_facet	Julia Nilsson Maria Hörnberg Anja Schmidt-Christensen Kajsa Linde Maria Nilsson Marine Carlus Saskia F. Erttmann Sofia Mayans Dan Holmberg
author_sort	Julia Nilsson
title	NKT cells promote both type 1 and type 2 inflammatory responses in a mouse model of liver fibrosis
title_short	NKT cells promote both type 1 and type 2 inflammatory responses in a mouse model of liver fibrosis
title_full	NKT cells promote both type 1 and type 2 inflammatory responses in a mouse model of liver fibrosis
title_fullStr	NKT cells promote both type 1 and type 2 inflammatory responses in a mouse model of liver fibrosis
title_full_unstemmed	NKT cells promote both type 1 and type 2 inflammatory responses in a mouse model of liver fibrosis
title_sort	nkt cells promote both type 1 and type 2 inflammatory responses in a mouse model of liver fibrosis
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/bddd626351e343c4987a764b323cded1
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_version_	1718384195876683776

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

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