Mucosal-associated invariant T cells are a profibrogenic immune cell population in the liver

Pushpa Hegde, Emmanuel Weiss, Valérie Paradis, Jinghong Wan, Morgane Mabire, Sukriti Sukriti, Pierre-Emmanuel Rautou, Miguel Albuquerque, Olivia Picq, Abhishak Chandra Gupta, Gladys Ferrere, Hélène Gilgenkrantz, Badr Kiaf, Amine Toubal, Lucie Beaudoin, Philippe Lettéron, Richard Moreau, Agnès Lehuen () and Sophie Lotersztajn ()
Additional contact information
Pushpa Hegde: Centre de Recherche sur l’Inflammation
Emmanuel Weiss: Centre de Recherche sur l’Inflammation
Valérie Paradis: Centre de Recherche sur l’Inflammation
Jinghong Wan: Centre de Recherche sur l’Inflammation
Morgane Mabire: Centre de Recherche sur l’Inflammation
Sukriti Sukriti: Centre de Recherche sur l’Inflammation
Pierre-Emmanuel Rautou: Assistance Publique-Hôpitaux de Paris
Miguel Albuquerque: Centre de Recherche sur l’Inflammation
Olivia Picq: Centre de Recherche sur l’Inflammation
Abhishak Chandra Gupta: Centre de Recherche sur l’Inflammation
Gladys Ferrere: Centre de Recherche sur l’Inflammation
Hélène Gilgenkrantz: Centre de Recherche sur l’Inflammation
Badr Kiaf: Université Paris-Descartes
Amine Toubal: Université Paris-Descartes
Lucie Beaudoin: Université Paris-Descartes
Philippe Lettéron: Centre de Recherche sur l’Inflammation
Richard Moreau: Centre de Recherche sur l’Inflammation
Agnès Lehuen: Université Paris-Descartes
Sophie Lotersztajn: Centre de Recherche sur l’Inflammation

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: Abstract Liver fibrosis is the common response to chronic liver injury, and leads to cirrhosis and its complications. Persistent inflammation is a driving force of liver fibrosis progression. Mucosal-associated invariant T (MAIT) cells are non-conventional T cells that display altered functions during chronic inflammatory diseases. Here, we show that circulating MAIT cells are reduced in patients with alcoholic or non-alcoholic fatty liver disease-related cirrhosis while they accumulate in liver fibrotic septa. Using two models of chronic liver injury, we demonstrate that MAIT cell-enriched mice show increased liver fibrosis and accumulation of hepatic fibrogenic cells, whereas MAIT cell-deficient mice are resistant. Co-culture experiments indicate that MAIT cells enhance the proinflammatory properties of monocyte-derived macrophages, and promote mitogenic and proinflammatory functions of fibrogenic cells, via distinct mechanisms. Our results highlight the profibrogenic functions of MAIT cells and suggest that targeting MAIT cells may constitute an attractive antifibrogenic strategy during chronic liver injury.

Date: 2018
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DOI: 10.1038/s41467-018-04450-y

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