Editorial: CD1- and MR1-Restricted T Cells in Antimicrobial Immunity

Haeryfar, S. M. Mansour; Mallevaey, Thierry

doi:10.3389/fimmu.2015.00611

Cited by 11 publications

(13 citation statements)

References 64 publications

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“…Mucosa‐associated invariant T (MAIT) cells have come under increasing scrutiny in recent years. They may fulfill protective or pathogenic functions in infectious diseases and malignancies . MAIT cells are best known for their immunomodulatory cytokine production capacity.…”

Section: Preamblementioning

confidence: 99%

MAIT cell-mediated cytotoxicity: Roles in host defense and therapeutic potentials in infectious diseases and cancer

Rudak

Choi

Haeryfar

2018

Journal of Leukocyte Biology

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Mucosa-associated invariant T (MAIT) cells are unconventional, innate-like T lymphocytes that sense the presence of MHC-related protein 1 (MR1)-restricted ligands and select inflammatory cues. Consequently, they release potent immunomodulatory mediators, including IFN-γ, TNF-α, and/or IL-17. MAIT cells can also be viewed as killer cells. They display several NK cell-associated receptors, carry granules containing cytotoxic effector molecules, and swiftly upregulate perforin and granzymes upon activation. Accordingly, MAIT cells are capable of lysing MR1-expressing cells infected with a variety of pathogenic bacteria in in vitro settings and may also mount cytotoxic responses during microbial infections in vivo. Of note, MAIT cell hyperactivation during certain infections may impede their ability to elicit inflammatory and/or cytotoxic responses to secondary stimuli. In addition, MAIT cells isolated from within and from the margin of tumor masses exhibit diminished functions. We propose that MAIT cell-mediated cytotoxicity can be induced, bolstered, or restored to assist in clearing infections and potentially in reducing tumor loads. In this review, we discuss our current understanding of MAIT cells' lytic functions and highlight the pressing questions that need to be addressed in future investigations. We also offer a picture, however hypothetical at this point, of how harnessing the full cytotoxic potentials of MAIT cells may be a valuable approach in the immunotherapy of infectious and malignant diseases.

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Section: Preamblementioning

confidence: 99%

MAIT cell-mediated cytotoxicity: Roles in host defense and therapeutic potentials in infectious diseases and cancer

Rudak

Choi

Haeryfar

2018

Journal of Leukocyte Biology

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“…Despite their rarity, NKT cell responses can drive inflammation or tolerance, thereby impacting a wide range of immune cells, such as dendritic cells, NK cells, and B and T cells (2). NKT cells protect their host organisms from certain strains of bacteria, sustain antiviral responses, and contribute to the suppression of certain types of cancer and immune diseases (1,(3)(4)(5)(6). In contrast, NKT cells are involved in the pathophysiology of allergic responses, ulcerative colitis, and liver cancer (7)(8)(9).…”

mentioning

confidence: 99%

Roquin Paralogs Differentially Regulate Functional NKT Cell Subsets

Drees

Vahl

Bortoluzzi

et al. 2017

The Journal of Immunology

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NKT cells represent a small subset of glycolipid-recognizing T cells that are heavily implicated in human allergic, autoimmune, and malignant diseases. In the thymus, precursor cells recognize self-glycolipids by virtue of their semi-invariant TCR, which triggers NKT cell lineage commitment and maturation. During their development, NKT cells are polarized into the NKT1, NKT2, and NKT17 subsets, defined through their cytokine-secretion patterns and the expression of key transcription factors. However, we have largely ignored how the differentiation into the NKT cell subsets is regulated. In this article, we describe the mRNAbinding Roquin-1 and-2 proteins as central regulators of murine NKT cell fate decisions. In the thymus, T cell-specific ablation of the Roquin paralogs leads to a dramatic expansion of NKT17 cells, whereas peripheral mature NKT cells are essentially absent. Roquin-1/2-deficient NKT17 cells show exaggerated lineage-specific expression of nearly all NKT17-defining proteins tested. We show through mixed bone marrow chimera experiments that NKT17 polarization is mediated through cell-intrinsic mechanisms early during NKT cell development. In contrast, the loss of peripheral NKT cells is due to cell-extrinsic factors. Surprisingly, Roquin paralog-deficient NKT cells are, in striking contrast to conventional T cells, compromised in their ability to secrete cytokines. Altogether, we show that Roquin paralogs regulate the development and function of NKT cell subsets in the thymus and periphery.

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“…25,26 These mediators enable MAIT cell participation in host defense and in immunoregulatory feedback and feedforward loops either to the benefit or to the detriment of the host. It is thus not surprising that protective or pathogenic roles for MAIT cells have been demonstrated or suggested in various diseases and conditions, including infectious diseases, [27][28][29] sepsis, 30 toxic shock, 31 allergy, 32 autoimmunity, 33 and malignancy. 34,35 Recent evidence suggests that MAIT cells can also operate in an MR1-dependent fashion to promote tissue repair.…”

Section: Mait Cells In Briefmentioning

confidence: 99%

MAIT Cells in COVID-19: Heroes, Villains, or Both?

Haeryfar

2020

Crit Rev Immunol

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Mucosa-associated invariant T cells (MAIT cells) are unconventional, innate-like T lymphocytes with remarkable effector and immunoregulatory functions. They are abundant in the human peripheral blood and also enriched in mucosal layers and in the lungs, SARS-CoV-2's main ports of entry. Once activated, MAIT cells produce inflammatory cytokines and cytolytic effector molecules quickly and copiously. MAIT cells are best known for their antibacterial and antifungal properties. However, they are also activated during viral infections, typically in a cytokine-dependent manner, which may promote antiviral immunity. On the other hand, it is plausible to assume active roles for MAIT cells in infection-provoked cytokine storms and tissue damage. SARS-CoV-2 infection may be asymptomatic, mild, severe, or even fatal, depending on sex, age, the presence of preexisting morbidities, and the individual's immunological competence, or lack thereof, among other factors. Based on the available literature, I propose that MAIT cells regulate the host response to SARS-CoV-2 and constitute attractive targets in the prevention or clinical management of coronavirus disease 19 (COVID-19) and some of its complications. Unlike mainstream T cells, MAIT cells are restricted by a monomorphic antigen-presenting molecule called MHC-related protein 1 (MR1). Therefore, MR1 ligands should modify MAIT cell functions relatively uniformly in genetically diverse subjects and may be tested as immunotherapeutic agents or vaccine adjuvants in future studies.

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Editorial: CD1- and MR1-Restricted T Cells in Antimicrobial Immunity

Cited by 11 publications

References 64 publications

MAIT cell-mediated cytotoxicity: Roles in host defense and therapeutic potentials in infectious diseases and cancer

MAIT cell-mediated cytotoxicity: Roles in host defense and therapeutic potentials in infectious diseases and cancer

Roquin Paralogs Differentially Regulate Functional NKT Cell Subsets

MAIT Cells in COVID-19: Heroes, Villains, or Both?

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