Human liver CD8+ MAIT cells exert TCR/MR1-independent innate-like cytotoxicity in response to IL-15

Rha, Min‐Seok; Han, Jiwon; Kim, Jong Hoon; Koh, June-Young; Park, Hye Jung; Kim, Soon Il; Kim, Myoung Soo; Lee, Jae Geun; Lee, Hyun Woong; Lee, Dong Hoon; Kim, Won; Park, Jun Yong; Joo, Dong Jin; Park, Su–Hyung; Shin, Eui‐Cheol

doi:10.1016/j.jhep.2020.03.033

Cited by 48 publications

(42 citation statements)

References 45 publications

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“…[71][72][73][74][75] MAIT cells can be activated indirectly by IL-12, IL-18, and IL-15 produced by other immune cells in the absence of TCR signaling. 76,77 Two key transcription factors, RORγt and promyelocytic leukemia zincfinger (PLZF), appear to be responsible for the distinctive phenotypes of MAIT cells. 78,79 The percentage of CD161 hi Vα7.2 + MAIT cells was significantly higher in the liver than in the blood (~15% of IHLs in the liver vs.~3% of PBLs in blood).…”

Section: Innate Lymphoid Cells (Ilcs)mentioning

confidence: 99%

“…70 Hepatic MAIT cells are generally more activated and display tissue residency with high levels of CD69, CD56, CD38, PD-1, and NKG2D expression. 77,85 MAIT cells resident in the liver adapt to exert their functions, such as dominantly producing IL-17A, which is licensed by IL-7 produced by hepatocytes in the context of inflammation. 81 Furthermore, liver MAIT cells can exert TCR/MR1-independent but NKG2D-dependent cytotoxicity in response to the cytokine IL-15.…”

Section: Innate Lymphoid Cells (Ilcs)mentioning

confidence: 99%

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Innate lymphocytes: pathogenesis and therapeutic targets of liver diseases and cancer

Chen

Tian

2020

Cell Mol Immunol

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The liver is a lymphoid organ with unique immunological properties, particularly, its predominant innate immune system. The balance between immune tolerance and immune activity is critical to liver physiological functions and is responsible for the sensitivity of this organ to numerous diseases, including hepatotropic virus infection, alcoholic liver disease, nonalcoholic fatty liver disease, autoimmune liver disease, and liver cancer, which are major health problems globally. In the past decade, with the discovery of liver-resident natural killer cells, the importance of innate lymphocytes with tissue residency has gradually become the focus of research. In this review, we address the current knowledge regarding hepatic innate lymphocytes with unique characteristics, including NK cells, ILC1/2/3s, NKT cells, γδ T cells, and MAIT cells, and their potential roles in liver homeostasis maintenance and the progression of liver diseases and cancer. A better understanding of the immunopathogenesis of hepatic innate lymphocytes will be helpful for proposing effective treatments for liver diseases and cancer.

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Section: Innate Lymphoid Cells (Ilcs)mentioning

confidence: 99%

Section: Innate Lymphoid Cells (Ilcs)mentioning

confidence: 99%

Innate lymphocytes: pathogenesis and therapeutic targets of liver diseases and cancer

Chen

Tian

2020

Cell Mol Immunol

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“…Alternatively, gated MAIT cells within PBMCs are analyzed after stimulation, either alone, or with cell lines or dendritic cells as APCs ( 11 , 28 , 46 , 124 , 135 – 137 ). Although a number of studies have examined the in vitro activation responses of MAIT cells sourced from human tissues ( 77 , 100 , 138 , 139 ) to our knowledge these have not been used for MR1 ligand identification purposes. The activation of cells in these assays has been assessed by upregulation of markers [e.g., CD69, CD25, CD137(41-BB)], down-regulation of CD3 and cytokine production.…”

Section: Tools For the Assessment Of Mr1 Ligand Production And Recognmentioning

confidence: 99%

Antigen Recognition by MR1-Reactive T Cells; MAIT Cells, Metabolites, and Remaining Mysteries

et al. 2020

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Mucosal-associated Invariant T (MAIT) cells recognize vitamin B-based antigens presented by the non-polymorphic MHC class I related-1 molecule (MR1). Both MAIT T cell receptors (TCR) and MR1 are highly conserved among mammals, suggesting an important, and conserved, immune function. For many years, the antigens they recognize were unknown. The discovery that MR1 presents vitamin B-based small molecule ligands resulted in a rapid expansion of research in this area, which has yielded information on the role of MAIT cells in immune protection, autoimmune disease and recently in homeostasis and cancer. More recently, we have begun to appreciate the diverse nature of the small molecule ligands that can bind MR1, with several less potent antigens and small molecule drugs that can bind MR1 being identified. Complementary structural information has revealed the complex nature of interactions defining antigen recognition. Additionally, we now view MAIT cells (defined here as MR1-riboflavin-Ag reactive, TRAV1-2 + cells) as one subset of a broader family of MR1-reactive T cells (MR1T cells). Despite these advances, we still lack a complete understanding of how MR1 ligands are generated, presented and recognized in vivo . The biological relevance of these MR1 ligands and the function of MR1T cells in infection and disease warrants further investigation with new tools and approaches.

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“…In mice, the MAIT TCR is composed of homologous gene segments, a TRAV1-TRAJ33 TCRα chain, that pairs with a TCRβ chain composed of TRBV19 or TRBV13 V gene segments, both of which are murine orthologous segments of human TRBV6 (3,5,10). MAIT cells are abundant in healthy adults, representing on average 3% of blood T cells (11) and can be found throughout peripheral tissues (6,7,10,(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23). The frequency of MAIT cells in laboratory mice is distinctly lower than in humans, although murine MAIT cells are also found in many peripheral organs (24,25).…”

Section: Introductionmentioning

confidence: 99%

Biased MAIT TCR Usage Poised for Limited Antigen Diversity?

Souter

Eckle

2020

Front. Immunol.

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Mucosal-associated invariant T (MAIT) cells are a subset of unconventional T cells that recognize the evolutionarily conserved major histocompatibility complex (MHC) class I-like antigen-presenting molecule known as MHC class I related protein 1 (MR1). Since their rise from obscurity in the early 1990s, the study of MAIT cells has grown substantially, accelerating our fundamental understanding of these cells and their possible roles in immunity. In the context of recent advances, we review here the relationship between MR1, antigen, and TCR usage among MAIT and other MR1-reactive T cells and provide a speculative discussion.

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Human liver CD8+ MAIT cells exert TCR/MR1-independent innate-like cytotoxicity in response to IL-15

Cited by 48 publications

References 45 publications

Innate lymphocytes: pathogenesis and therapeutic targets of liver diseases and cancer

Innate lymphocytes: pathogenesis and therapeutic targets of liver diseases and cancer

Antigen Recognition by MR1-Reactive T Cells; MAIT Cells, Metabolites, and Remaining Mysteries

Biased MAIT TCR Usage Poised for Limited Antigen Diversity?

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