The effects of 5‐OP‐RU stereochemistry on its stability and MAIT‐MR1 axis

Matsuoka, Takuro; Motozono, Chihiro; Hattori, Akira; Kakeya, Hideaki; Yamasaki, Satoshi; Oishi, Shinya; Ohno, Hiroaki; Inuki, Shinsuke

doi:10.1002/cbic.202000466

Cited by 12 publications

(19 citation statements)

References 29 publications

(56 reference statements)

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“…Mucosal‐associated invariant T cells (MAIT) are gut resident innate immune cells that play an important role in gut inflammation and defence against pathogen infection. Bacterial riboflavin‐derived antigen, 5‐OP‐RU, was found to be able to travel from mucosal surfaces to the thymus and be taken up by the major histocompatibility complex class I‐related protein (MR1) to promote the generation of MAIT 81,82 . Consequently, early life exposure to microbial riboflavin can regulate the development of and also interact with MAIT cells, to promote gut immunity and homeostasis 83 .…”

Section: Microbiota Are Involved In the Development Of The Nervous An...mentioning

confidence: 99%

“…Bacterial riboflavin‐derived antigen, 5‐OP‐RU, was found to be able to travel from mucosal surfaces to the thymus and be taken up by the major histocompatibility complex class I‐related protein (MR1) to promote the generation of MAIT. 81 , 82 Consequently, early life exposure to microbial riboflavin can regulate the development of and also interact with MAIT cells, to promote gut immunity and homeostasis. 83 The SCFA butyrate, a major gut metabolite, has also been found to facilitate either the differentiation of T regulatory cells or effector T helper‐1 cells under different conditions, suggesting that the influence of gut microbiota on the differentiation of immune cells is subjected to the local environment.…”

Section: Microbiota Are Involved In the Development Of The Nervous An...mentioning

confidence: 99%

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Importance of crosstalk between the microbiota and the neuroimmune system for tissue homeostasis

Mehta

et al. 2022

Clin & Trans Imm

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The principal function of inflammation is cellular defence against ‘danger signals’ such as tissue injury and pathogen infection to maintain the homeostasis of the organism. The initiation and progression of inflammation are not autonomous as there is substantial evidence that inflammation is known to be strongly influenced by ‘neuroimmune crosstalk’, involving the production and expression of soluble signalling molecules that interact with cell surface receptors. In addition, microbiota have been found to be involved in the development and function of the nervous and immune systems and play an important role in health and disease. Herein, we provide an outline of the mechanisms of neuroimmune communication in the regulation of inflammation and immune response and then provide evidence for the involvement of microbiota in the development and functions of the host nervous and immune systems. It appears that the nervous and immune systems in multicellular organisms have co‐evolved with the microbiota, such that all components are in communication to maximise the ability of the organism to adapt to a wide range of environmental stresses to maintain or restore tissue homeostasis.

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Section: Microbiota Are Involved In the Development Of The Nervous An...mentioning

confidence: 99%

Section: Microbiota Are Involved In the Development Of The Nervous An...mentioning

confidence: 99%

Importance of crosstalk between the microbiota and the neuroimmune system for tissue homeostasis

Mehta

et al. 2022

Clin & Trans Imm

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“…Three major populations of innate T cells are recognized, namely, mucosal-associated invariant T (MAIT) cells, invariant natural killer T (iNKT) cells, and gamma delta T (γδT) cells [ 7 , 8 ]. MAIT cells are antibacterial immune cells that target invasive bacterial pathogens through the MAIT TCR recognition of unstable bacterial pyrimidines presented by the MHC class I-related gene protein (MR1) [ 9 , 10 ]. This allows them to have an MHC-independent response against bacterial invaders [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

“…MAIT cells are antibacterial immune cells that target invasive bacterial pathogens through the MAIT TCR recognition of unstable bacterial pyrimidines presented by the MHC class I-related gene protein (MR1) [ 9 , 10 ]. This allows them to have an MHC-independent response against bacterial invaders [ 10 ]. In a similar but distinctively unique fashion, iNKT cells recognize the presentation of both self and non-self lipid antigens by CD1d on antigen-presenting cells (APCs) [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

“…In a similar but distinctively unique fashion, iNKT cells recognize the presentation of both self and non-self lipid antigens by CD1d on antigen-presenting cells (APCs) [ 11 ]. These cells combine innate and adaptive immune characteristics, making them a sort of “hybrid” immune cell that has the adaptive advantages of typical αβ T cells and the rapid response of innate immunity [ 10 , 12 ]. The third innate T cells are γδT cells, which have a γδ TCR instead of the conventional αβ TCR, making them MHC-independent and allowing for an innate immune response to tumor-associated antigens and non-peptidic antigens [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

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Targeting Immunosuppressive Tumor-Associated Macrophages Using Innate T Cells for Enhanced Antitumor Reactivity

Brown

et al. 2022

Cancers

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The field of T cell-based and chimeric antigen receptor (CAR)-engineered T (CAR-T) cell-based antitumor immunotherapy has seen substantial developments in the past decade; however, considerable issues, such as graft-versus-host disease (GvHD) and tumor-associated immunosuppression, have proven to be substantial roadblocks to widespread adoption and implementation. Recent developments in innate immune cell-based CAR therapy have opened several doors for the expansion of this therapy, especially as it relates to allogeneic cell sources and solid tumor infiltration. This study establishes in vitro killing assays to examine the TAM-targeting efficacy of MAIT, iNKT, and γδT cells. This study also assesses the antitumor ability of CAR-engineered innate T cells, evaluating their potential adoption for clinical therapies. The in vitro trials presented in this study demonstrate the considerable TAM-killing abilities of all three innate T cell types, and confirm the enhanced antitumor abilities of CAR-engineered innate T cells. The tumor- and TAM-targeting capacity of these innate T cells suggest their potential for antitumor therapy that supplements cytotoxicity with remediation of tumor microenvironment (TME)-immunosuppression.

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Potent Immunomodulators Developed from an Unstable Bacterial Metabolite of Vitamin B2 Biosynthesis

Mak,

Rivero,

Hoang

et al. 2024

Angewandte Chemie

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Bacterial synthesis of vitamin B2 generates a by‐product, 5‐(2‐oxopropylideneamino)‐d‐ribityl‐aminouracil (5‐OP‐RU), with potent immunological properties in mammals, but rapid inactivation in water limits practical uses. This natural product covalently bonds to immunological protein MR1 in antigen presenting cells (APCs), enabling MR1 to traffic to the cell surface, where it interacts with T cell receptors (TCRs) on mucosal associated invariant T lymphocytes (MAIT cells), activating their immunological and antimicrobial properties. Here, we develop several new series of water‐stable compounds tailored for powerful and distinctive immunological functions. We report their water stability, capacity to bind MR1 and traffic it to the cell surface (EC50 17 nM), potent activation (EC50 56 pM) or inhibition (IC50 80 nM) of interacting MAIT cells, and develop compounds with diazirine‐alkyne, biotin, or fluorophore labels for studying cellular MR1. Computer modelling casts new light on the molecular mechanism of activation, revealing that activators are first captured in MR1 via pi‐interactions and H‐bonds, before tighter covalent bonding to Lys43 in MR1. This chemical study advances our molecular understanding of how bacterial metabolites are captured by MR1, influence cell surface expression of MR1, interact and modify human T cells; offering new clues for developing novel vaccine adjuvants, immunotherapeutics, and cancer drugs.

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The effects of 5‐OP‐RU stereochemistry on its stability and MAIT‐MR1 axis

Cited by 12 publications

References 29 publications

Importance of crosstalk between the microbiota and the neuroimmune system for tissue homeostasis

Importance of crosstalk between the microbiota and the neuroimmune system for tissue homeostasis

Targeting Immunosuppressive Tumor-Associated Macrophages Using Innate T Cells for Enhanced Antitumor Reactivity

Potent Immunomodulators Developed from an Unstable Bacterial Metabolite of Vitamin B2 Biosynthesis

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