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On the immunoregulatory role of statins in multiple sclerosis: the effects on Th17 cells

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Abstract

Statins, the cholesterol-lowering drugs, also possess immunomodulatory properties, affecting among others T cell activation and differentiation, antigen presentation, and regulatory T cell (Tregs) maintenance and differentiation. Their effects on autoagression have led investigators to assess their clinical significance in autoimmune disease, such as multiple sclerosis (MS), a chronic progressive demyelinating disease of autoimmune nature. The dysregulated immunity noted in MS features a profound shift from Tregs dominance to Th17 cell superiority. In this review, we discuss the immunobiological basis of statins, their role in autoimmunity related to MS, and the data from experimental models and human studies on their effect on Th17 cells.

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Abbreviations

APC:

Antigen-presenting cell

BBB:

Blood–brain barrier

CSF:

Cerebrospinal fluid

EDSS:

Expanded Disability Status Scale

FACS:

Fluorescence-activated cell sorting

FoxP3:

Forkhead box P3

IFN:

Interferon

IL:

Interleukin

mAb:

Monoclonal antibodies

MBP:

Myelin basic protein

MS:

Multiple sclerosis

NMO:

Neuromyelitis optica

PB:

Peripheral blood

PBMC:

Peripheral blood mononuclear cells

RORC:

Retinoid-related orphan receptor C

RRMS:

Relapsing-remitting MS

SPMS:

Secondary progressive MS

T-bet:

T-box expressed in T cells

TGF:

Transforming growth factor

Th:

T-helper

TNF:

Tumor necrosis factor

Treg:

T regulatory cells

VLA:

Very late antigen

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  1. Department of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University General Hospital of Larissa, University of Thessaly, Biopolis, 40500, Larissa, Greece

    Georgios Ntolkeras, Chrysanthi Barba, Athanasios Mavropoulos, Georgios K. Vasileiadis, Lazaros I. Sakkas & Dimitrios P. Bogdanos

  2. Department of Neurology and Laboratory of Neurogenetics, Faculty of Medicine, School of Health Sciences, University General Hospital of Larissa, University of Thessaly, Viopolis, 40500, Larissa, Greece

    Efthymios Dardiotis & Georgios Hadjigeorgiou

  3. Department of Neurology, University of Cyprus Medical School, Nicosia, Cyprus

    Georgios Hadjigeorgiou

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Ntolkeras, G., Barba, C., Mavropoulos, A. et al. On the immunoregulatory role of statins in multiple sclerosis: the effects on Th17 cells. Immunol Res 67, 310–324 (2019). https://doi.org/10.1007/s12026-019-09089-5

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