Mucosal-Associated Invariant T Cells in Multiple Sclerosis: The Jury is Still Out

The immune system is strongly implicated in the pathophysiology of multiple sclerosis (MS), as demonstrated by the efficacy of therapies targeting various components of adaptive immunity. However, the disease still progresses despite these treatments in many patients, while others experience life-th...

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Published inFrontiers in immunology Vol. 6; p. 503
Main Authors Treiner, Emmanuel, Liblau, Roland S.
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers 30.09.2015
Frontiers Media S.A
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ISSN1664-3224
1664-3224
DOI10.3389/fimmu.2015.00503

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Abstract The immune system is strongly implicated in the pathophysiology of multiple sclerosis (MS), as demonstrated by the efficacy of therapies targeting various components of adaptive immunity. However, the disease still progresses despite these treatments in many patients, while others experience life-threatening adverse effects, urging for the discovery of new immune-targeting medications. Among the immune cell types participating to MS pathogenesis, decades of work have highlighted the prominent role of CD4 T cells. More recent data demonstrate the involvement of CD8 T cells as well. The existence of both pathogenic and protective CD8 T cells subsets has been suggested, adding an additional layer of complexity to the picture. Mucosal-associated invariant T (MAIT) cells are innate-like lymphocytes that make up to 25% of CD8 T cells in healthy subjects. They are specific for conserved microbial ligands and may constitute an important barrier against invasive bacterial and fungal infection. An increasing number of reports also suggest their possible involvement in chronic inflammatory diseases, including MS. MAIT cells could participate through their ability to produce IFNγ and/or IL-17, two major cytokines in the pathogenesis of several chronic inflammatory/autoimmune diseases. However, the mechanisms by which MAIT cells could be activated in these sterile conditions are not known. Furthermore, contradictory observations have been made, reporting either a protective or a pro-inflammatory behavior of MAIT cells in MS or its murine model, experimental autoimmune encephalomyelitis. In this review article, we will describe the current knowledge on MAIT cell biology in health and disease, and discuss the possible mechanisms behind their role in MS. The specific features of this new non-conventional T cell subset make it an interesting candidate as a biomarker or as the target of immune-mediated intervention.
AbstractList The immune system is strongly implicated in the pathophysiology of multiple sclerosis (MS), as demonstrated by the efficacy of therapies targeting various components of adaptive immunity. However, the disease still progresses despite these treatments in many patients, while others experience life-threatening adverse effects, urging for the discovery of new medications targeting other pathways. Decades of work have highlighted the prominent role of CD4 T cells in MS, but more recent data demonstrate the involvement of CD8 T cells as well. The existence of both pathogenic and protective CD8 T cells subsets has been suggested, adding an additional layer of complexity to the picture. Mucosal-Associated Invariant T cells (MAIT) are innate-like lymphocytes that make up to 25% of CD8 T cells in healthy subjects. They are specific for conserved microbial ligands and may constitute an important barrier against invasive bacterial and fungal infection. An increasing number of reports also suggest their possible involvement in chronic inflammatory diseases, including MS. MAIT cells could participate through their ability to produce IFNgamma and/or IL-17, two major cytokines in the pathogenesis of several chronic inflammatory/autoimmune diseases. However, the mechanisms by which MAIT cells could be activated in these sterile conditions are not known. Furthermore, contradictory observations have been made, reporting either a protective or a pro-inflammatory behavior of MAIT cells in MS or its murine model, experimental autoimmune encephalomyelitis (EAE). In this review article, we will describe the current knowledge on MAIT cells biology in health and disease, and discuss the possible mechanisms behind their role in MS. The specific features of this new nonconventional T cell subset make it an interesting candidate as a biomarker or as the target of immune-mediated intervention.
The immune system is strongly implicated in the pathophysiology of multiple sclerosis (MS), as demonstrated by the efficacy of therapies targeting various components of adaptive immunity. However, the disease still progresses despite these treatments in many patients, while others experience life-threatening adverse effects, urging for the discovery of new immune-targeting medications. Among the immune cell types participating to MS pathogenesis, decades of work have highlighted the prominent role of CD4 T cells. More recent data demonstrate the involvement of CD8 T cells as well. The existence of both pathogenic and protective CD8 T cells subsets has been suggested, adding an additional layer of complexity to the picture. Mucosal-associated invariant T (MAIT) cells are innate-like lymphocytes that make up to 25% of CD8 T cells in healthy subjects. They are specific for conserved microbial ligands and may constitute an important barrier against invasive bacterial and fungal infection. An increasing number of reports also suggest their possible involvement in chronic inflammatory diseases, including MS. MAIT cells could participate through their ability to produce IFNγ and/or IL-17, two major cytokines in the pathogenesis of several chronic inflammatory/autoimmune diseases. However, the mechanisms by which MAIT cells could be activated in these sterile conditions are not known. Furthermore, contradictory observations have been made, reporting either a protective or a pro-inflammatory behavior of MAIT cells in MS or its murine model, experimental autoimmune encephalomyelitis. In this review article, we will describe the current knowledge on MAIT cell biology in health and disease, and discuss the possible mechanisms behind their role in MS. The specific features of this new non-conventional T cell subset make it an interesting candidate as a biomarker or as the target of immune-mediated intervention.
The immune system is strongly implicated in the pathophysiology of multiple sclerosis (MS), as demonstrated by the efficacy of therapies targeting various components of adaptive immunity. However, the disease still progresses despite these treatments in many patients, while others experience life-threatening adverse effects, urging for the discovery of new immune-targeting medications. Among the immune cell types participating to MS pathogenesis, decades of work have highlighted the prominent role of CD4 T cells. More recent data demonstrate the involvement of CD8 T cells as well. The existence of both pathogenic and protective CD8 T cells subsets has been suggested, adding an additional layer of complexity to the picture. Mucosal-associated invariant T (MAIT) cells are innate-like lymphocytes that make up to 25% of CD8 T cells in healthy subjects. They are specific for conserved microbial ligands and may constitute an important barrier against invasive bacterial and fungal infection. An increasing number of reports also suggest their possible involvement in chronic inflammatory diseases, including MS. MAIT cells could participate through their ability to produce IFNγ and/or IL-17, two major cytokines in the pathogenesis of several chronic inflammatory/autoimmune diseases. However, the mechanisms by which MAIT cells could be activated in these sterile conditions are not known. Furthermore, contradictory observations have been made, reporting either a protective or a pro-inflammatory behavior of MAIT cells in MS or its murine model, experimental autoimmune encephalomyelitis. In this review article, we will describe the current knowledge on MAIT cell biology in health and disease, and discuss the possible mechanisms behind their role in MS. The specific features of this new non-conventional T cell subset make it an interesting candidate as a biomarker or as the target of immune-mediated intervention.The immune system is strongly implicated in the pathophysiology of multiple sclerosis (MS), as demonstrated by the efficacy of therapies targeting various components of adaptive immunity. However, the disease still progresses despite these treatments in many patients, while others experience life-threatening adverse effects, urging for the discovery of new immune-targeting medications. Among the immune cell types participating to MS pathogenesis, decades of work have highlighted the prominent role of CD4 T cells. More recent data demonstrate the involvement of CD8 T cells as well. The existence of both pathogenic and protective CD8 T cells subsets has been suggested, adding an additional layer of complexity to the picture. Mucosal-associated invariant T (MAIT) cells are innate-like lymphocytes that make up to 25% of CD8 T cells in healthy subjects. They are specific for conserved microbial ligands and may constitute an important barrier against invasive bacterial and fungal infection. An increasing number of reports also suggest their possible involvement in chronic inflammatory diseases, including MS. MAIT cells could participate through their ability to produce IFNγ and/or IL-17, two major cytokines in the pathogenesis of several chronic inflammatory/autoimmune diseases. However, the mechanisms by which MAIT cells could be activated in these sterile conditions are not known. Furthermore, contradictory observations have been made, reporting either a protective or a pro-inflammatory behavior of MAIT cells in MS or its murine model, experimental autoimmune encephalomyelitis. In this review article, we will describe the current knowledge on MAIT cell biology in health and disease, and discuss the possible mechanisms behind their role in MS. The specific features of this new non-conventional T cell subset make it an interesting candidate as a biomarker or as the target of immune-mediated intervention.
Author Liblau, Roland S.
Treiner, Emmanuel
AuthorAffiliation 3 Department of Immunology, Toulouse University Hospital , Toulouse , France
1 Centre de Physiopathologie de Toulouse-Purpan (CPTP), INSERM UMR1043-CNRS 5282 , Toulouse , France
2 Université Toulouse III - Paul-Sabatier , Toulouse , France
AuthorAffiliation_xml – name: 2 Université Toulouse III - Paul-Sabatier , Toulouse , France
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Keywords IFN gamma
innate-like T cells
MHC-related 1
multiple sclerosis
adaptive immunity
Language English
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Edited by: Manu Rangachari, Centre Hospitalier Universitaire de Québec, Canada
Reviewed by: Hiroshi Wakao, Hokkaido University, Japan; Manuel Friese, Universitätsklinikum Hamburg-Eppendorf, Germany
Specialty section: This article was submitted to Multiple Sclerosis and Neuroimmunology, a section of the journal Frontiers in Immunology
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Snippet The immune system is strongly implicated in the pathophysiology of multiple sclerosis (MS), as demonstrated by the efficacy of therapies targeting various...
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SubjectTerms Adaptive Immunity
IFN gamma
Immunology
innate like T cells
Life Sciences
MHC-Related 1
Multiple Sclerosis
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Title Mucosal-Associated Invariant T Cells in Multiple Sclerosis: The Jury is Still Out
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