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

Hegde, Pushpa; Weiss, Emmanuel; Paradis, Valérie; Wan, Jinghong; Mabire, Morgane; Sukriti, Sukriti; Rautou, Pierre‐Emmanuel; Albuquerque, Miguel; Picq, Olivia; Gupta, Abhishak; Ferrere, Gladys; Gilgenkrantz, Hélène; Kiaf, Badr; Toubal, Amine; Beaudoin, Lucie; Lettéron, Philippe; Moreau, Richard; Lehuen, Agnès; Lotersztajn, Sophie

doi:10.1038/s41467-018-04450-y

Cited by 167 publications

(233 citation statements)

References 50 publications

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“…In the case of PSC, and except for the actual inflammation in the liver that could promote gut leakiness, many patients also have concomitant IBD. Interestingly, loss in circulation and accumulation of MAIT cells in inflamed intestine has previously been reported in IBD patients where level of MAIT cells also correlated with disease activity . Yet, we observed no significant differences regarding the MAIT cell loss in patients with PSC and IBD compared to patients with PSC only.…”

Section: Resultscontrasting

confidence: 47%

Primary sclerosing cholangitis leads to dysfunction and loss of MAIT cells

et al. 2018

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Primary sclerosing cholangitis (PSC) is a severe chronic liver disease of the small and large bile ducts. The pathogenesis is unknown but a strong immune cell component has been suggested. Mucosal-associated invariant T (MAIT) cells are abundant in human liver and localize around bile ducts. Yet, the role of MAIT cells in PSC remains unclear.Here, we performed a detailed characterization of MAIT cells in circulation and assessed their presence in bile ducts of PSC patients as well as non-PSC controls. We observed a dramatic reduction in MAIT cell levels in PSC patients. High-dimensional phenotypical analysis using stochastic neighbor embedding revealed the MAIT cells to be activated, a phenotype shared by the investigated disease control groups. In line with the noted phenotypic alterations, MAIT cell function was reduced in response to Escherichia coli and to cytokine stimulation in PSC patients as compared to healthy controls. Using a novel sampling approach of human bile ducts, we found MAIT cells to be specifically enriched within bile ducts. Finally, distinct from the dramatic decline observed in circulation, PSCpatients had retained levels of MAIT cells within bile ducts. Altogether, our results provide a detailed insight into how the human MAIT cell compartment is affected in PSC.Keywords: Gut-liver axis r Inflammation r Inflammatory bowel disease r Mucosal-associated invariant T cells r Primary sclerosing cholangitis Additional supporting information may be found online in the Supporting Information section at the end of the article.

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Section: Resultscontrasting

confidence: 47%

Primary sclerosing cholangitis leads to dysfunction and loss of MAIT cells

et al. 2018

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“…MAIT cells can contribute to cytokine release from macrophages (23) and have shown to promote inflammatory monocyte differentiation into dendritic cells during pulmonary infection (24). Thus, we next sought to determine the cause of reduced tissue cytokine production of MR1 -/mice during sepsis.…”

Section: Mait Deficiency Is Associated With Reduced Tissue-specific Imentioning

confidence: 99%

Mucosal-associated invariant T (MAIT) cells mediate protective host responses in sepsis

Trivedi

Labuz

Anderson

et al. 2020

Preprint

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Sepsis is a systemic inflammatory response to infection and a leading cause of death. Mucosal-associated invariant T (MAIT) cells are innate-like T cells enriched in mucosal tissues that recognize bacterial ligands. We investigated MAIT cells during clinical and experimental sepsis, and their contribution to host responses. In experimental sepsis, MAIT-deficient mice had significantly increased mortality and bacterial load, and reduced tissue-specific cytokine responses. MAIT cells of WT mice expressed lower levels of IFN-γ and IL-17a during sepsis compared to sham surgery, changes not seen in non-MAIT T cells. MAIT cells of patients presenting with sepsis were significantly reduced in frequency, more activated, and had decreased IFN-γ production when stimulated, compared to healthy donors and paired 90-day post-sepsis samples. Our data suggest that MAIT cells are highly activated and become dysfunctional during clinical sepsis, and contribute to tissue-specific cytokine responses that are protective against mortality during experimental sepsis.

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“…Conversely, once stimulated, ILC2s secrete IL‐13 and IL‐4, which activate HSCs and stimulate LF. More recently, innate‐like T lymphocytes, which include iNKT cells and MAIT cells, have emerged as accelerators of inflammation and fibrosis during CCL 4 ‐ or BDL‐induced liver injury . However, the definitive roles played by these innate‐like lymphocytes in the pathogenesis of NASH remain unknown.…”

Section: Innate Immune Cellular Players In Nashmentioning

confidence: 99%

The Role of Innate Immune Cells in Nonalcoholic Steatohepatitis

2019

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Inflammation and metabolic dysfunction are hallmarks of nonalcoholic steatohepatitis (NASH), which is one of the fastest‐growing liver diseases worldwide. Emerging evidence indicates that innate immune mechanisms are pivotal drivers of inflammation and other pathological manifestations observed in NASH, such as hepatosteatosis, insulin resistance (IR), and fibrosis. This robust innate immune reaction is intrinsic to the liver, which is an important immunological organ that contains a coordinated network of innate immune cells, including Kupffer cells (KCs), dendritic cells (DCs), and lymphocytes. Hepatocytes and liver sinusoidal endothelial cells (LSECs) are not formally innate immune cells, but they take on immune cell function when stressed. These cells can sense excess metabolites and bacterial products and translate those signals into immune responses and pathological hepatic changes during the development of NASH. In this review, we take a historical perspective in describing decades of research that aimed to identify the key molecular and cellular players in the innate immune system in the setting of NASH. Furthermore, we summarize the innate immune cells that are involved in the progression of NASH and illustrate how they sense disturbances in circulating metabolic factors by innate immune receptors and subsequently initiate the intercellular signaling cascades that lead to persistent inflammation and progression of hepatic complications.

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

Cited by 167 publications

References 50 publications

Primary sclerosing cholangitis leads to dysfunction and loss of MAIT cells

Primary sclerosing cholangitis leads to dysfunction and loss of MAIT cells

Mucosal-associated invariant T (MAIT) cells mediate protective host responses in sepsis

The Role of Innate Immune Cells in Nonalcoholic Steatohepatitis

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