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Immune Cell Contributors to the Female Sex Bias in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

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Sex Differences in Brain Function and Dysfunction

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 62))

Abstract

Multiple sclerosis (MS) is a chronic, autoimmune, demyelinating disease of the central nervous system (CNS) that leads to axonal damage and accumulation of disability. Relapsing-remitting MS (RR-MS) is the most frequent presentation of MS and this form of MS is three times more prevalent in females than in males. This female bias in MS is apparent only after puberty, suggesting a role for sex hormones in this regulation; however, very little is known of the biological mechanisms that underpin the sex difference in MS onset. Experimental autoimmune encephalomyelitis (EAE) is an animal model of RR-MS that presents more severely in females in certain mouse strains and thus has been useful to study sex differences in CNS autoimmunity. Here, we overview the immunopathogenesis of MS and EAE and how immune mechanisms in these diseases differ between a male and female. We further describe how females exhibit more robust myelin-specific T helper (Th) 1 immunity in MS and EAE and how this sex bias in Th cells is conveyed by sex hormone effects on the T cells, antigen presenting cells, regulatory T cells, and innate lymphoid cell populations.

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Abbreviations

Aire:

Autoimmune regulator

APC:

Antigen presenting cell

BBB:

Blood-brain barrier

cDC:

Classical dendritic cell

CFA:

Complete Freund’s adjuvant

CNS:

Central nervous system

CSF:

Cerebrospinal fluid

DC:

Dendritic cell

DC1:

Type 1 classical dendritic cell

DC2:

Type 2 classical dendritic cell

E2:

17-beta-estradiol

EAE:

Experimental autoimmune encephalomyelitis

Gd:

Gadolinium

GM-CSF:

Granulocyte-macrophage colony-stimulating factor

GWAS:

Genome-wide susceptibility study

IFN:

Interferon

Ig:

Immunoglobulin

IL:

Interleukin

ILC2:

Type 2 innate lymphoid cell

LPS:

Lipopolysaccharide

MBP:

Myelin basic protein

MHC:

Major histocompatibility complex

MHC-II:

Major histocompatibility complex class II

MMP:

Matrix metalloproteinase

MOG:

Myelin oligodendrocyte glycoprotein

MRI:

Magnetic resonance imaging

MS:

Multiple sclerosis

NK:

Natural killer cell

NKT:

Natural killer T cell

PLP:

Myelin proteolipid protein

PPAR:

Peroxisome proliferator-activated receptor

PP-MS:

Primary progressive multiple sclerosis

PTX:

Pertussis toxin

RR-MS:

Relapsing-remitting multiple sclerosis

S1PR:

Sphingosine-1-phosphate receptor

SP-MS:

Secondary progressive multiple sclerosis

TCR:

T cell receptor

TEC:

Thymic epithelial cell

Th:

T helperspiepr146 cell

TLR:

Toll-like receptor

TMEV:

Theiler’s murine encephalomyelitis virus

TNF:

Tumour necrosis factor

Tr1:

Type I regulatory cell

Treg:

T regulatory cell

TSPO-PET:

18-kDa translocator protein positron emission tomography

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Authors and Affiliations

  1. Keenan Research Centre for Biomedical Science, St. Michael’s Hospital, Toronto, ON, Canada

    Nuria Alvarez-Sanchez & Shannon E. Dunn

  2. Department of Immunology, University of Toronto, Toronto, ON, Canada

    Nuria Alvarez-Sanchez & Shannon E. Dunn

  3. Women’s College Research Institute, Toronto, ON, Canada

    Shannon E. Dunn

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  1. Nuria Alvarez-Sanchez
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  2. Shannon E. Dunn
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Correspondence to Shannon E. Dunn .

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  1. School of Psychology, University of Nottingham, Nottingham, UK

    Claire Gibson

  2. Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada

    Liisa A. M. Galea

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Alvarez-Sanchez, N., Dunn, S.E. (2022). Immune Cell Contributors to the Female Sex Bias in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis. In: Gibson, C., Galea, L.A.M. (eds) Sex Differences in Brain Function and Dysfunction. Current Topics in Behavioral Neurosciences, vol 62. Springer, Cham. https://doi.org/10.1007/7854_2022_324

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