Mucosal-associated invariant T cells from induced pluripotent stem cells: A novel approach for modeling human diseases

Sugimoto, Chie; Fujita, Hideaki; Wakao, Hiroshi

doi:10.4252/wjsc.v8.i4.158

Cited by 8 publications

(8 citation statements)

References 106 publications

(163 reference statements)

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“…We initially compared the circulating levels of Mucosal-associated invariant T (MAIT) cells in BAV versus TAV cases with and without TAA. MAIT cells represent a novel innate-like T cell subsets consisting of 1%–10% of T cells in the peripheral blood [ 18 – 20 ]. They mediate a pivotal role in immune-dysregulated diseases and other pathologies, like infections, inflammatory diseases, and others [ 18 – 20 ].…”

Section: Resultsmentioning

confidence: 99%

“…MAIT cells represent a novel innate-like T cell subsets consisting of 1%–10% of T cells in the peripheral blood [ 18 – 20 ]. They mediate a pivotal role in immune-dysregulated diseases and other pathologies, like infections, inflammatory diseases, and others [ 18 – 20 ]. We observed that the mean blood levels of MAIT cells, expressed in absolute numbers, were significantly different between the BAV and the TAV groups, with and without TAA (see Figure 1(a) ).…”

Section: Resultsmentioning

confidence: 99%

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A Typical Immune T/B Subset Profile Characterizes Bicuspid Aortic Valve: In an Old Status?

Balistreri

Buffa

Allegra

et al. 2018

Oxidative Medicine and Cellular Longevity

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Bicuspid valve disease is associated with the development of thoracic aortic aneurysm. The molecular mechanisms underlying this association still need to be clarified. Here, we evaluated the circulating levels of T and B lymphocyte subsets associated with the development of vascular diseases in patients with bicuspid aortic valve or tricuspid aortic valve with and without thoracic aortic aneurysm. We unveiled that the circulating levels of the MAIT, CD4+IL−17A+, and NKT T cell subsets were significantly reduced in bicuspid valve disease cases, when compared to tricuspid aortic valve cases in either the presence or the absence of thoracic aortic aneurysm. Among patients with tricuspid aortic valve, these cells were higher in those also affected by thoracic aortic aneurysm. Similar data were obtained by examining CD19+ B cells, naïve B cells (IgD+CD27−), memory unswitched B cells (IgD+CD27+), memory switched B cells (IgD−CD27+), and double-negative B cells (DN) (IgD−CD27−). These cells resulted to be lower in subjects with bicuspid valve disease with respect to patients with tricuspid aortic valve. In whole, our data indicate that patients with bicuspid valve disease show a quantitative reduction of T and B lymphocyte cell subsets. Future studies are encouraged to understand the molecular mechanisms underlying this observation and its pathophysiological significance.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

A Typical Immune T/B Subset Profile Characterizes Bicuspid Aortic Valve: In an Old Status?

Balistreri

Buffa

Allegra

et al. 2018

Oxidative Medicine and Cellular Longevity

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“…The state of immunoparesis characteristic of patients with ALD, especially patients with SAH, may be intensified by the combination of quantitative MAIT cell depletion and functional defects associated with the residual MAIT cell population. Ex vivo functionally reprogrammed MAIT cells, 14 51 MAIT cells derived from induced pluripotent stem cells (iPSC-derived MAIT cells) 60 and strategies aimed at restoring the gut barrier may represent novel attractive immunotherapeutic avenues for cirrhosis and alcoholic liver disease.…”

Section: Discussionmentioning

confidence: 99%

Mucosa-associated invariant T cells link intestinal immunity with antibacterial immune defects in alcoholic liver disease

Riva

Patel

Kurioka

et al. 2017

Gut

121

168

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Background/aimsIntestinal permeability with systemic distribution of bacterial products are central in the immunopathogenesis of alcoholic liver disease (ALD), yet links with intestinal immunity remain elusive. Mucosa-associated invariant T cells (MAIT) are found in liver, blood and intestinal mucosa and are a key component of antibacterial host defences. Their role in ALD is unknown.Methods/designWe analysed frequency, phenotype, transcriptional regulation and function of blood MAIT cells in severe alcoholic hepatitis (SAH), alcohol-related cirrhosis (ARC) and healthy controls (HC). We also examined direct impact of ethanol, bacterial products from faecal extracts and antigenic hyperstimulation on MAIT cell functionality. Presence of MAIT cells in colon and liver was assessed by quantitative PCR and immunohistochemistry/gene expression respectively.ResultsIn ARC and SAH, blood MAIT cells were dramatically depleted, hyperactivated and displayed defective antibacterial cytokine/cytotoxic responses. These correlated with suppression of lineage-specific transcription factors and hyperexpression of homing receptors in the liver with intrahepatic preservation of MAIT cells in ALD. These alterations were stronger in SAH, where surrogate markers of bacterial infection and microbial translocation were higher than ARC. Ethanol exposure in vitro, in vivo alcohol withdrawal and treatment with Escherichia coli had no effect on MAIT cell frequencies, whereas exposure to faecal bacteria/antigens induced functional impairments comparable with blood MAIT cells from ALD and significant MAIT cell depletion, which was not observed in other T cell compartments.ConclusionsIn ALD, the antibacterial potency of MAIT cells is compromised as a consequence of contact with microbial products and microbiota, suggesting that the ‘leaky’ gut observed in ALD drives MAIT cell dysfunction and susceptibility to infection in these patients.

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“…Drugs have the promise of achieving the MAIT cell response appropriate for the individual disease as an agonist or antagonist of MAIT cell activity. Other therapeutic possibilities are ex vivo re-programming of MAIT cell function with select cytokines[ 82 , 107 ], vaccination with IL-23 in combination with 5-OP-RU[ 217 ], and re-programming and re-differentiating MAIT cells using induced pluripotent stem cells derived from MAIT cells[ 223 ]. Glucocorticoids reduce MAIT cell frequency in certain immune-mediated diseases[ 15 , 177 , 185 ], and they also may have a role in modulating MAIT cell activity.…”

Section: Incorporating Mait Cells Into the Pathogenesis Of Chronic Liver Diseasementioning

confidence: 99%

Incorporating mucosal-associated invariant T cells into the pathogenesis of chronic liver disease

Czaja

2021

WJG

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Mucosal-associated invariant T (MAIT) cells have been described in liver and non-liver diseases, and they have been ascribed antimicrobial, immune regulatory, protective, and pathogenic roles. The goals of this review are to describe their biological properties, indicate their involvement in chronic liver disease, and encourage investigations that clarify their actions and therapeutic implications. English abstracts were identified in PubMed by multiple search terms, and bibliographies were developed. MAIT cells are activated by restricted non-peptides of limited diversity and by multiple inflammatory cytokines. Diverse pro-inflammatory, anti-inflammatory, and immune regulatory cytokines are released; infected cells are eliminated; and memory cells emerge. Circulating MAIT cells are hyper-activated, immune exhausted, dysfunctional, and depleted in chronic liver disease. This phenotype lacks disease-specificity, and it does not predict the biological effects. MAIT cells have presumed protective actions in chronic viral hepatitis, alcoholic hepatitis, non-alcoholic fatty liver disease, primary sclerosing cholangitis, and decompensated cirrhosis. They have pathogenic and pro-fibrotic actions in autoimmune hepatitis and mixed actions in primary biliary cholangitis. Local factors in the hepatic microenvironment (cytokines, bile acids, gut-derived bacterial antigens, and metabolic by-products) may modulate their response in individual diseases. Investigational manipulations of function are warranted to establish an association with disease severity and outcome. In conclusion, MAIT cells constitute a disease-nonspecific, immune response to chronic liver inflammation and infection. Their pathological role has been deduced from their deficiencies during active liver disease, and future investigations must clarify this role, link it to outcome, and explore therapeutic interventions.

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Mucosal-associated invariant T cells from induced pluripotent stem cells: A novel approach for modeling human diseases

Cited by 8 publications

References 106 publications

A Typical Immune T/B Subset Profile Characterizes Bicuspid Aortic Valve: In an Old Status?

A Typical Immune T/B Subset Profile Characterizes Bicuspid Aortic Valve: In an Old Status?

Mucosa-associated invariant T cells link intestinal immunity with antibacterial immune defects in alcoholic liver disease

Incorporating mucosal-associated invariant T cells into the pathogenesis of chronic liver disease

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