MAIT cells: potent major cellular players in the IL-17 pathway of spondyloarthritis?

Toussirot, Éric; Saas, Philippe

doi:10.1136/rmdopen-2018-000821

Cited by 12 publications

(7 citation statements)

References 36 publications

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“…We complement and expand these findings by reporting an inverse association of canonical (TCRVa7.2 + ) circulating MR1-tet + CD4 + CD8and CD4 + CD8 + , but not CD4 -CD8 + and CD4 -CD8 -, or MR1-restricted TCRVa7.2 -T cells with PV, adding to a growing body of literature on immune cell aberrations in PV. These cells exhibit sex-based differences in the prevalence of TRAV1-2 + sets (47), and their canonical CD4 -CD8 ± fractions commonly decline among adult PBMC in response to various (auto)inflammatory processes (68)(69)(70), and aging (47,71). In this context, it is significant that stimulation of MAIT cells may itself result in TCRVa7.2 downregulation, potentially affecting subsequent detection by flow cytometry (72,73), but this has yet to be demonstrated in vivo.…”

Section: Discussionmentioning

confidence: 99%

Differential Skewing of Circulating MR1-Restricted and γδ T Cells in Human Psoriasis Vulgaris

et al. 2020

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Psoriasis vulgaris (PV) is a chronic, recurrent inflammatory dermatosis mediated by aberrantly activated immune cells. The role of the innate-like T cells, particularly gammadelta T (γδT) cells and MR1-restricted T lymphocytes, is incompletely explored, mainly through animal models, or by use of surrogate lineage markers, respectively. Here, we used case-control settings, multiparameter flow cytometry, 5-OP-RU-loaded MR1-tetramers, Luminex technology and targeted qRT-PCR to dissect the cellular and transcriptional landscape of γδ and MR1-restricted blood T cells in untreated PV cases (n=21, 22 matched controls). High interpersonal differences in cell composition were observed, fueling transcriptional variability at healthy baseline. A minor subset of canonical CD4+CD8+MR1-tet+TCRVα7.2+ and CD4+CD8-MR1-tet+TCRVα7.2+ T cells was the most significantly underrepresented community in male PV individuals, whereas Vδ2+ γδ T cells expressing high levels of TCR and Vδ1-δ2- γδ T cells expressing intermediate levels of TCR were selectively enriched in affected males, partly reflecting disease severity. Our findings highlight a formerly unappreciated skewing of human circulating MAIT and γδ cytomes during PV, and reveal their compositional changes in relation to sex, CMV exposure, serum cytokine content, BMI, and inflammatory burden. Complementing numerical alterations, we finally show that flow-sorted, MAIT and γδ populations exhibit divergent transcriptional changes in mild type I psoriasis, consisting of differential bulk expression for signatures of cytotoxicity/type-1 immunity (EOMES, RUNX3, IL18R), type-3 immunity (RORC, CCR6), and T cell innateness (ZBTB16).

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Section: Discussionmentioning

confidence: 99%

Differential Skewing of Circulating MR1-Restricted and γδ T Cells in Human Psoriasis Vulgaris

et al. 2020

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“…The importance of these cells in axial-SpA pathogenesis and their gastrointestinal predominant origin further underlines the tight connection existing between joint and gut inflammation often found in these patients [ 8 ]. MAIT could be activated through two different pathways: (1) recognition of the monomorphic MHC class-1 related protein MR1 bound to nonpeptide antigens by the semi-invariant MAIT TCR or (2) cytokine stimulation upon receptor expressed on their cellular surface such as IL-7R, IL-23R, IL-12R, and IL18R [ 86 ]. MAIT concentrations in PB from AS patients are decreased, at the same time being increased in inflamed tissues such as SF of inflamed joints.…”

Section: Role Of Innate Immunitymentioning

confidence: 99%

Uncovering the Underworld of Axial Spondyloarthritis

Vescovo

Venerito

Iannone

et al. 2023

IJMS

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Axial spondyloarthritis (axial-SpA) is a multifactorial disease characterized by inflammation in sacroiliac joints and spine, bone reabsorption, and aberrant bone deposition, which may lead to ankylosis. Disease pathogenesis depends on genetic, immunological, mechanical, and bioenvironmental factors. HLA-B27 represents the most important genetic factor, although the disease may also develop in its absence. This MHC class I molecule has been deeply studied from a molecular point of view. Different theories, including the arthritogenic peptide, the unfolded protein response, and HLA-B27 homodimers formation, have been proposed to explain its role. From an immunological point of view, a complex interplay between the innate and adaptive immune system is involved in disease onset. Unlike other systemic autoimmune diseases, the innate immune system in axial-SpA has a crucial role marked by abnormal activity of innate immune cells, including γδ T cells, type 3 innate lymphoid cells, neutrophils, and mucosal-associated invariant T cells, at tissue-specific sites prone to the disease. On the other hand, a T cell adaptive response would seem involved in axial-SpA pathogenesis as emphasized by several studies focusing on TCR low clonal heterogeneity and clonal expansions as well as an interindividual sharing of CD4/8 T cell receptors. As a result of this immune dysregulation, several proinflammatory molecules are produced following the activation of tangled intracellular pathways involved in pathomechanisms of axial-SpA. This review aims to expand the current understanding of axial-SpA pathogenesis, pointing out novel molecular mechanisms leading to disease development and to further investigate potential therapeutic targets.

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“…Other immune cells, including mast cells and macrophages, can further amplify the inflammatory effect by secreting cytokines such as IL-23, IL-17, IL-1, IL-22, and tumor necrosis factor (TNF)-α ( Annunziato et al., 2015 ). MAIT cells are capable of producing pro-inflammatory cytokines, such as IL-17, IL-22, TNF, or interferon (IFN)-γ ( Gracey et al., 2016 ; Toussirot and Saas, 2018 ; Li et al., 2022 ). Taken together, these findings show that various immune cell-mediated IL-23/IL-17 axes contribute to the migration of blood vessels.…”

Section: Mechanisms Of Microbiota-derived Intestinal Inflammation In Spamentioning

confidence: 99%

Emerging story of gut dysbiosis in spondyloarthropathy: From gastrointestinal inflammation to spondyloarthritis

Liu

Chen

Gao

et al. 2022

Front. Cell. Infect. Microbiol.

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As a set of inflammatory disorders, spondyloarthritis (SpA) exhibits distinct pathophysiological, clinical, radiological, and genetic characteristics. Due to the extra-articular features of this disorder, early recognition is crucial to limiting disability and improving outcomes. Gut dysbiosis has been linked to SpA development as evidence grows. A pathogenic SpA process is likely to occur when a mucosal immune system interacts with abnormal local microbiota, with subsequent joint involvement. It is largely unknown, however, how microbiota alterations predate the onset of SpA within the “gut-joint axis”. New microbiome therapies, such as probiotics, are used as an adjuvant therapy in the treatment of SpA, suggesting that the modulation of intestinal microbiota and/or intestinal barrier function may contribute to the prevention of SpA. In this review, we highlight the mechanisms of SpA by which the gut microbiota impacts gut inflammation and triggers the activation of immune responses. Additionally, we analyze the regulatory role of therapeutic SpA medication in the gut microbiota and the potential application of probiotics as adjunctive therapy for SpA.

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MAIT cells: potent major cellular players in the IL-17 pathway of spondyloarthritis?

Cited by 12 publications

References 36 publications

Differential Skewing of Circulating MR1-Restricted and γδ T Cells in Human Psoriasis Vulgaris

Differential Skewing of Circulating MR1-Restricted and γδ T Cells in Human Psoriasis Vulgaris

Uncovering the Underworld of Axial Spondyloarthritis

Emerging story of gut dysbiosis in spondyloarthropathy: From gastrointestinal inflammation to spondyloarthritis

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