The Immune Modulating Properties of Mucosal-Associated Invariant T Cells

Abstract

Mucosal-associated invariant T (MAIT) cells are unconventional T lymphocytes that express a semi-invariant T cell receptor (TCR) recognizing microbial vitamin B metabolites presented by the highly conserved major histocompatibility complex (MHC) class I like molecule, MR1. The vitamin B metabolites are produced by several commensal and pathogenic bacteria and yeast, but not viruses. Nevertheless, viral infections can trigger MAIT cell activation in a TCR-independent manner, through the release of pro-inflammatory cytokines by antigen-presenting cells (APCs). MAIT cells belong to the innate like T family of cells with a memory phenotype, which allows them to rapidly release Interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and in some circumstances Interleukin (IL)-17 and IL-10, exerting an immunomodulatory role on the ensuing immune response, akin to iNKT cells and γδ T cells. Recent studies implicate MAIT cells in a variety of inflammatory, autoimmune diseases, and in cancer. In addition, through the analysis of the transcriptome of MAIT cells activated in different experimental conditions, an important function in tissue repair and control of immune homeostasis has emerged, shared with other innate-like T cells. In this review, we discuss these recent findings, focussing on the understanding of the molecular mechanisms underpinning MAIT cell activation and effector function in health and disease, which ultimately will aid in clinically harnessing this unique, not donor-restricted cell subtype.

Bifidobacteria-mediated immune system imprinting early in life

“…Lacking Bifidobacteriaceae was associated with expanded populations of neutrophils, basophils, plasmablasts, and memory CD8 + T cells, indicating both innate and adaptive immune activation (Figure 3A). Mucosal associated invariant T cells (MAIT) are important T cells in the intestinal response to bacterial vitamin B metabolites (Ioannidis et al, 2020) and these were also more abundant in blood from children with a low abundance of Bifidobacteriaceae (Figure 3A). Conversely, children with abundant gut Bifidobacteriaceae had higher frequency of non-classical monocytes, often considered as anti-inflammatory (Narasimhan et al, 2019), as well as antigen-experienced regulatory T cells expressing the CD39 receptor, a highly suppressive Treg subset (Gu et al, 2017) (Figure 3A).…”

Gut Microbiota Comparison Between Intestinal Contents and Mucosa in Mice With Repeated Stress-Related Diarrhea Provides Novel Insight

“…In healthy people, the intestinal mucosa is the site of continual interactions between microbes, tissue cells, and the immune system ( Seo et al, 2020 ). A latest finding was reported that mucosal-associated invariant T (MAIT) cells interact with local microbiota and integrate multiple signals, so it plays an important role in local inflammation ( Ioannidis et al, 2020 ). The microbiome at homeostasis colonized in intestinal mucosa can antagonize pathogenic bacteria, clear endotoxin, and play a role of resistance to external environmental factors ( Seo et al, 2020 ); in turn, the intestinal epithelial cells can also affect the community structure of intestinal mucosal microbiota ( Yoo et al, 2020 ).…”

IL-33 Enhances IFNγ and TNFα Production by Human MAIT Cells: A New Pro-Th1 Effect of IL-33

“…MAIT cells can be stimulated in a TCR-dependent and TCR-independent manner [ 1 , 2 , 3 , 4 , 9 , 17 , 18 ]. IL-12 associated with IL-18 has been described as activating MAIT cells independently of the TCR [ 9 ].…”