Mucosa-associated invariant T (MAIT) cells are the largest population of unconventional T cells in humans. These antimicrobial T cells are poised with rapid effector responses following recognition of the cognate riboflavin (vitamin B)-like metabolite antigens derived from microbial riboflavin biosynthetic pathway. Presentation of this unique class of small molecule metabolite antigens is mediated by the highly evolutionarily conserved major histocompatibility complex class I-related protein. In humans, MAIT cells are widely found along the upper and lower gastrointestinal tracts owing to their high expression of chemokine receptors and homing molecules directing them to these tissue sites. In this review, we discuss recent findings regarding the roles MAIT cells play in various gastrointestinal bacterial infections, and how their roles appear to differ depending on the etiological agents and the anatomical location. We further discuss the potential mechanisms by which MAIT cells contribute to pathogen control, orchestrate adaptive immunity, as well as their potential contribution to inflammation and tissue damage during gastrointestinal bacterial infections, and the ensuing tissue repair following resolution. Finally, we propose and discuss the use of the emerging three-dimensional organoid technology to test different hypotheses regarding the role of MAIT cells in gastrointestinal bacterial infections, inflammation, and immunity.
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http://dx.doi.org/10.1016/j.mucimm.2023.06.005 | DOI Listing |
Immunity
December 2024
Experimental Immunology, Department of Biomedicine, University Hospital Basel, University of Basel, 4031 Basel, Switzerland. Electronic address:
The major histocompatibility complex (MHC) class I-related molecule MHC-class-I-related protein 1 (MR1) presents metabolites to distinct MR1-restricted T cell subsets, including mucosal-associated invariant T (MAIT) and MR1T cells. However, self-reactive MR1T cells and the nature of recognized antigens remain underexplored. Here, we report a cell endogenous carbonyl adduct of adenine (8-(9H-purin-6-yl)-2-oxa-8-azabicyclo[3.
View Article and Find Full Text PDFFront Immunol
December 2024
Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy.
Background: The phosphodiesterase 4 (PDE4) inhibitor apremilast downregulates the production of IL-23 and other pro-inflammatory cytokines involved in the pathogenesis of psoriatic arthritis (PsA).
Aim: To investigate the effects of apremilast on the production of cytokines by peripheral blood monocyte-derived macrophages, innate-like lymphocyte cells (ILCs), mucosal-associated invariant T (MAIT) cells, γδ T cells, natural killer (NK) cells, and NKT-like cells from patients with PsA manifesting different clinical responses to the treatment.
Methods: Peripheral blood samples were obtained from patients with PsA at baseline and after 1 and 4 months of apremilast therapy (n = 23) and 20 controls with osteoarthritis.
Cell Mol Life Sci
December 2024
Department of Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
ENPP1/CD203a is a membrane-bound ectonucleotidase capable of hydrolyzing ATP, cGAMP and other substrates. Its enzymatic activity plays an important role in the balance of extracellular adenine nucleotides and the modulation of purinergic signaling, in soft tissue calcification, and in the regulation of the cGAS/STING pathway. However, a detailed analysis of ENPP1 surface expression on human immune cells has not been performed.
View Article and Find Full Text PDFHuman immune systems are highly variable, with most variation attributable to non-genetic sources. The gut microbiome crucially shapes the immune system; however, its relationship with the baseline immune states of healthy humans remains incompletely understood. Therefore, we performed multi-omic profiling of 110 healthy participants through the ImmunoMicrobiome study.
View Article and Find Full Text PDFCancer Cell
December 2024
Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Parker Institute for Cancer Immunotherapy, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address:
Unconventional T cells, including invariant natural killer T (iNKT) cells, gamma delta (γδ) T cells, and mucosal-associated invariant T (MAIT) cells, play important roles in both innate and adaptive immunity. These cells respond to tumors rapidly and influence the tumor microenvironment (TME). Recent advances in understanding their biology, as well as the development of novel therapeutic approaches, have underscored their potential in cancer immunotherapy.
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