Persistent reduction of mucosal‐associated invariant T cells in primary biliary cholangitis

Setsu, Toru; Yamagiwa, Satoshi; Tominaga, Kentaro; Kimura, Naruhiro; Honda, Hiroki; Kamimura, Hiroteru; Tsuchiya, Atsunori; Takamura, Masaaki; Terai, Shuji

doi:10.1111/jgh.14076

Cited by 25 publications

(36 citation statements)

References 34 publications

(94 reference statements)

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“…This finding is consistent with previous studies that reported reduced abundance of MAIT cells in peripheral blood 10,25 and in liver tissues 10 of PBC patients compared to healthy controls. Setsu et al observed that depleted MAIT cells were not recovered to normal levels in the blood of PBC patients even after UDCA treatment, suggesting the possibility that MAIT cells were being activated, exhausted, and depleted due to ongoing liver inflammation 10 . Along those lines, the reducedabundance CD8 + CD161 + T cell metacluster in our study also expressed high levels of the immune-exhaustion biomarker PD-1, and one of the constituent clusters expressed high-levels of CTLA4, which is also a marker of exhaustion.…”

Section: Discussionsupporting

confidence: 94%

Single-Cell Mass Cytometry on Peripheral Blood Identifies Immune Cell Subsets Associated with Primary Biliary Cholangitis

Jang

Juran

Cunningham

et al. 2020

Preprint

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The relationship between Primary Biliary Cholangitis (PBC), a chronic cholestatic autoimmune liver disease, and the peripheral immune system remains to be fully understood. Herein, we performed the first mass cytometry (CyTOF)-based, immunophenotyping analysis of the peripheral immune system in PBC at single-cell resolution. CyTOF was performed on peripheral blood mononuclear cells (PBMCs) from PBC patients (n=33) and age-/sex-matched healthy controls (n=33) to obtain immune cell abundance and marker expression profiles. Hiearchical clustering methods were applied to identify immune cell types and subsets significantly associated with PBC. Subsets of gamma-delta T cells (CD3 + TCRgd + ), CD8 + T cells (CD3 + CD8 + CD161 + PD1 + ), and memory B cells (CD3 -CD19 + CD20 + CD24 + CD27 + ) were found to have lower abundance in PBC than in control. In contrast, higher abundance of subsets of monocytes and naïve B cells were observed in PBC compared to control. Furthermore, several naïve B cell (CD3 -CD19 + CD20 + CD24 -CD27 -) subsets were significantly higher in PBC patients with cirrhosis (indicative of late-stage disease) than in those without cirrhosis. Alternatively, subsets of CD8 + CD161 + T cells and memory B cells were lower in abundance in cirrhotic relative to non-cirrhotic PBC patients.Future immunophenotyping investigations could lead to better understanding of PBC pathogenesis and progression, and also to the discovery of novel biomarkers and treatment strategies.

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Section: Discussionsupporting

confidence: 94%

Single-Cell Mass Cytometry on Peripheral Blood Identifies Immune Cell Subsets Associated with Primary Biliary Cholangitis

Jang

Juran

Cunningham

et al. 2020

Preprint

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“…They also summarized the granzyme B expression by MAIT cells correlated with the fibrosis. Setsu et al [76] focused on the PBC patients. MAIT cells were obviously reduced, along with expressing lower levels of activation markers CD69 and IL-7 receptor.…”

Section: Autoimmune Liver Diseasementioning

confidence: 99%

Mucosal-Associated Invariant T cell in liver diseases

Zhang¹,

Kong²,

Wang³

2020

Int. J. Biol. Sci.

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Mucosal-associated invariant T cells (MAIT cells) are a new population of innate immune cells, which are abundant in the liver and play complex roles in various liver diseases. In this review, we summarize MAIT cells in the liver diseases in recent studies, figure out the role of MAIT cells in various liver disease, including Alcoholic liver disease, Non-alcoholic liver disease, Autoimmune liver diseases, Viral hepatitis and Liver Cancer. Briefly, MAIT cells are involved in anti-bacteria responses in the alcoholic liver diseases. Besides, the activated MAIT cells promote the liver inflammation by secreting inflammatory cytokines and produce regulatory cytokines, which induces anti-inflammatory macrophage polarization. MAIT cells participate in the liver fibrosis via enhancing hepatic stellate cell activation. In viral hepatitis, MAIT cells exhibit a flawed and exhausted phenotype, which results in little effect on controlling the virus and bacteria. In liver cancer, MAIT cells indicate the disease progression and the outcome of therapy. In summary, MAIT cells are attractive biomarkers and therapeutic targets for liver disease.

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“…In hepatocellular carcinoma (HCC) patients, peripheral blood MAIT cells are numerically and functionally depleted [86]. Similar discoveries were made in terms of several chronic inflammatory conditions that are associated with an increased risk of malignant transformation in the liver, namely hepatitis C virus (HCV) infection [87], primary biliary cholangitis [88], and alcoholic and non-alcoholic fatty liver disease [89]. The degree of MAIT cell deficiency corresponded with disease progression, measured as HCC advancement, extent of liver fibrosis, or serum level of liver damage markers.…”

Section: Hepatic Malignanciesmentioning

confidence: 74%

MAIT Cells Come to the Rescue in Cancer Immunotherapy?

Łukasik

Elewaut

Venken

2020

Cancers

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Recent progress in immunobiology has led to the observation that, among cells classically categorized as the typical representatives of the adaptive immune system, i.e., T cells, some possess the phenotype of innate cells. Invariant T cells are characterized by T cell receptors recognizing a limited range of non-peptide antigens, presented only in the context of particular molecules. Mucosal-associated invariant T cells (MAIT cells) are an example of such unconventional cells. In humans, they constitute between 1% and 8% of the peripheral blood T lymphocytes and are further enriched in mucosal tissues, mesenteric lymph nodes, and liver, where they can account for even 40% of all the T cells. MAIT cells recognize antigens in the context of major histocompatibility complex class I-related protein (MR1). Upon activation, they instantly release pro-inflammatory cytokines and mediate cytolytic function towards bacterially infected cells. As such, they have been a rapidly evolving research topic not only in the field of infectious diseases but also in the context of many chronic inflammatory diseases and, more recently, in immuno-oncology. Novel findings suggest that MAIT cells function could also be modulated by endogenous ligands and drugs, making them an attractive target for therapeutic approaches. In this review, we summarize the current understanding of MAIT cell biology, their role in health and disease and discuss their future potential in cancer immunotherapy. This is discussed through the prism of knowledge and experiences with invariant natural killer T cells (iNKT)—another prominent unconventional T cell subset that shares many features with MAIT cells.

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Persistent reduction of mucosal‐associated invariant T cells in primary biliary cholangitis

Abstract: These findings suggested that MAIT cells were activated, exhausted, and persistently depleted in PBC patients even after ursodeoxycholic acid treatment, possibly as a consequence of persistent liver inflammation.

Cited by 25 publications

References 34 publications

Single-Cell Mass Cytometry on Peripheral Blood Identifies Immune Cell Subsets Associated with Primary Biliary Cholangitis

Single-Cell Mass Cytometry on Peripheral Blood Identifies Immune Cell Subsets Associated with Primary Biliary Cholangitis

Mucosal-Associated Invariant T cell in liver diseases

MAIT Cells Come to the Rescue in Cancer Immunotherapy?

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