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; Sophie Lotersztajn

doi:10.1038/s41467-018-04450-y

Journal articles

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

Pushpa Hegde ^{1, 2} Emmanuel Weiss ^{1, 2, 3} Valérie Paradis ^{1, 2, 4} Jinghong Wan ^{1, 2} Morgane Mabire ^{1, 2} Sukriti Sukriti ^{1, 2} Pierre-Emmanuel Rautou ⁵ Miguel Albuquerque ^{1, 2, 4} Olivia Picq ^{1, 2} Abhishak Chandra Gupta ^{1, 2} Gladys Ferrere ^{1, 2} Hélène Gilgenkrantz ^{1, 2} Badr Kiaf ⁶ Amine Toubal ⁶ Lucie Beaudoin ⁶ Philippe Lettéron ^{1, 2} Richard Moreau ^{1, 2, 5} Agnès Lehuen ^{6, *} Sophie Lotersztajn ^{1, 2, 5, *}

* Corresponding author

1 CRI (UMR_S_1149 / ERL_8252 / U1149) - Centre de recherche sur l'Inflammation

2 Faculté de Médecine Xavier Bichat - Laboratoire d'Excellence Inflamex [Paris]

3 Département d'Anesthésie et Réanimation [Hôpital Beaujon]

4 Département de Pathologie [Hôpital Beaujon]

5 Service d'hépatologie [Hôpital Beaujon]

6 IC UM3 (UMR 8104 / U1016) - Institut Cochin

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.

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Journal articles

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Life Sciences [q-bio] / Immunology

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Submitted on : Wednesday, October 30, 2019 - 2:35:33 PM
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Mucosal-associated invariant T cells are a profibrogenic immune cell population in the liver

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