Neuropathologic, phenotypic and functional analyses of Mucosal Associated Invariant T cells in Multiple Sclerosis

Salou, Marion; Nicol, Bryan; García, Alexandra; Báron, Daniel; Michel, Laure; Elong-Ngono, Annie; Hulin, Philippe; Nédellec, Steven; Jacq-Foucher, Marylène; Frère, Fabienne Le; Jousset, Natacha; Bourreille, Arnaud; Wiertlewski, Sandrine; Soulillou, Jean‐Paul; Brouard, Sophie; Nicot, Arnaud; Degauque, Nicolas; Laplaud, David‐Axel

doi:10.1016/j.clim.2016.03.014

Cited by 52 publications

(65 citation statements)

References 54 publications

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“…A recent study confirmed the decreased blood MAIT cell frequency in MS patients with progressive disease as compared to healthy controls and remitting‐relapsing patients. However, this decrease could reflect the older age of progressive patients compared to the relapsing ones . In agreement with previous reports, MAIT cells harbored a migratory phenotype, CCR5 hi , CD49d + , CD58 + (LFA3), and in MS patients they expressed higher surface expression of CD11a (LFA‐1) and CD162 (PSGL‐1).…”

Section: Multiple Sclerosissupporting

confidence: 91%

“…Analysis of the canonical Vα7.2‐Jα33 TCRα chain by qPCR showed that MAIT cells are accumulated in some of the CNS lesions of MS and they are detected in a large majority of the cerebrospinal fluid samples obtained during relapse of MS . More recently, immunostaining analyses confirmed the presence of CD3 + CD161 + Va7.2 + MAIT cells in MS lesions where they can represent up to 3% of CD3 + cells.…”

Section: Multiple Sclerosismentioning

confidence: 94%

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Mucosal‐associated invariant T cells in autoimmune and immune‐mediated diseases

Rouxel

Lehuen

2018

Immunol Cell Biol

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Autoimmune and inflammatory diseases have complex etiologies not fully understood. Both innate and adaptive immune cells are involved in the pathogenesis of these diseases. Mucosal-associated invariant T (MAIT) cells express an invariant TCRα chain (Vα7.2-Jα33 in humans and Vα19-Jα33 in mice) and recognize the conserved MHC-I-related molecule MR1 presenting bacterial metabolites derived from the synthesis of vitamin B. MAIT cells harbor tissue homing properties and produce inflammatory cytokines, suggesting that MAIT cells may play a key role in autoimmune and inflammatory diseases. In this review, we described the current knowledge on MAIT cells in these pathologies, based on patients analyses as well as mouse models. While most of the studies support a deleterious role of MAIT cells in tissue inflammation and destruction, a few reports suggest a protective role of MAIT cells. MAIT cells could represent a new biomarker of disease progression, and a better knowledge of their function might open new avenues for therapeutic strategies based on their manipulation.

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Section: Multiple Sclerosissupporting

confidence: 91%

Section: Multiple Sclerosismentioning

confidence: 94%

Mucosal‐associated invariant T cells in autoimmune and immune‐mediated diseases

Rouxel

Lehuen

2018

Immunol Cell Biol

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“…In addition to intestinal inflammatory conditions, MAIT cells may also have a role in arthritic diseases, as they have been shown to exacerbate collagen‐induced arthritis, 79 whereas depletion of blood MAIT cells has also been reported in patients with systemic lupus erythromatosis and rheumatoid arthritis 31 , 53 . Various reports have also associated MAIT cells with multiple sclerosis, with the presence of MAIT cells in multiple sclerosis lesions confirmed by immunohistochemistry, 77 , 80 , 81 although both regulatory and pathogenic roles have been implicated 80 , 82 …”

Section: Mait Cells and Diseasementioning

confidence: 99%

“…In particular relevance to the liver, however, a number of studies have linked MAIT cells with intestinal inflammation. For instance, reduced frequencies of MAIT cells have been consistently demonstrated in the blood of patients with inflammatory bowel disease (both Crohn's disease and ulcerative colitis), 32 , 75 , 76 , 77 although there are conflicting findings between studies in the frequency of MAIT cells within the inflamed tissues 32 , 75 , 76 . MAIT cell frequencies are also altered in coeliac disease, where MAIT cells are depleted from the blood and gut 78 .…”

Section: Mait Cells and Diseasementioning

confidence: 99%

MAIT cells: new guardians of the liver

et al. 2016

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The liver is an important immunological organ that remains sterile and tolerogenic in homeostasis, despite continual exposure to non-self food and microbial-derived products from the gut. However, where intestinal mucosal defenses are breached or in the presence of a systemic infection, the liver acts as a second 'firewall', because of its enrichment with innate effector cells able to rapidly respond to infections or tissue dysregulation. One of the largest populations of T cells within the human liver are mucosal-associated invariant T (MAIT) cells, a novel innate-like T-cell population that can recognize a highly conserved antigen derived from the microbial riboflavin synthesis pathway. MAIT cells are emerging as significant players in the human immune system, associated with an increasing number of clinical diseases of bacterial, viral, autoimmune and cancerous origin. As reviewed here, we are only beginning to investigate the potential role of this dominant T-cell subset in the liver, but the reactivity of MAIT cells to both inflammatory cytokines and riboflavin derivatives suggests that MAIT cells may have an important role in first line of defense as part of the liver firewall. As such, MAIT cells are promising targets for modulating the host defense and inflammation in both acute and chronic liver diseases.

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“…MAIT cells can also be activated indirectly by IL-12 and IL18[22]. MAIT cells have been implicated in the immunopathogenesis of chronic viral infections like HIV[23, 24] and HCV[25, 26] and in inflammatory conditions like systemic lupus erythematosus[27] and MS[28, 29]. Therefore, we hypothesized that HTLV-1 infection is associated with defect in MAIT cells that could explain the increased susceptibility to Mtb.…”

Section: Introductionmentioning

confidence: 99%

MAIT cells are reduced in frequency and functionally impaired in human T lymphotropic virus type 1 infection: Potential clinical implications

et al. 2017

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HTLV-1 infection is associated with several inflammatory disorders, including the neurodegenerative condition HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). It is unclear why a minority of infected subjects develop HAM/TSP. The cellular immune response has been implicated in the development of inflammatory alterations in these patients; however the pathogenic mechanisms for disease progression remain unclear. Furthermore, HTLV-1-infected individuals have an increase incidence of Mycobacterium tuberculosis (Mtb) infection, suggesting that immunological defect are associated with HTLV-1 infection. Evidence suggests an important role for Mucosal-associated invariant T (MAIT) cells in the early control of Mtb infection. Chronic viral infections like HIV and HCV have been associated with decreased frequency and functionality of MAIT cells. We hypothesized that HTLV-1 infection is associated with similar perturbations in MAIT cells. We investigated MAIT cell frequency, phenotype, and function by flow cytometry in a cohort of 10 asymptomatic and 10 HAM/TSP HTLV-1 infected patients. We found that MAIT cells from HTLV-1-infected subjects were reduced and showed high co-expression of the activation markers CD38 and HLA-DR but normal levels of CCR6 and CD127. MAIT cells had a lower expression of the transcription factor PLZF in HAM/TSP patients. Unlike Tax-specific CD8+T cells, which are hyperfunctional, MAIT cells from HTLV-1-infected subjects had a poor IFNγ response following antigen stimulation. MAIT cell perturbations in HTLV-1 infection were not associated with HTLV-1 proviral load and MAIT cells were not infected by HTLV-1 in vivo. Rather, MAIT cells loss was associated with immune activation. Overall, our results do not support a role for MAIT cells in HAM/TSP pathogenesis but reduced numbers of MAIT cells, together with their poor functionality, could contribute to the increased susceptibility of HTLV-1-infected individuals to other infectious agents.

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Neuropathologic, phenotypic and functional analyses of Mucosal Associated Invariant T cells in Multiple Sclerosis

Cited by 52 publications

References 54 publications

Mucosal‐associated invariant T cells in autoimmune and immune‐mediated diseases

Mucosal‐associated invariant T cells in autoimmune and immune‐mediated diseases

MAIT cells: new guardians of the liver

MAIT cells are reduced in frequency and functionally impaired in human T lymphotropic virus type 1 infection: Potential clinical implications

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