TY - JOUR

T1 - The immunology of multiple sclerosis

AU - Attfield, Kathrine E.

AU - Jensen, Lise Torp

AU - Kaufmann, Max

AU - Friese, Manuel A.

AU - Fugger, Lars

PY - 2022

Y1 - 2022

N2 - Our incomplete understanding of the causes and pathways involved in the onset and progression of multiple sclerosis (MS) limits our ability to effectively treat this complex neurological disease. Recent studies explore the role of immune cells at different stages of MS and how they interact with cells of the central nervous system (CNS). The findings presented here begin to question the exclusivity of an antigen-specific cause and highlight how seemingly distinct immune cell types can share common functions that drive disease. Innovative techniques further expose new disease-associated immune cell populations and reinforce how environmental context is critical to their phenotype and subsequent role in disease. Importantly, the differentiation of immune cells into a pathogenic state is potentially reversible through therapeutic manipulation. As such, understanding the mechanisms that provide plasticity to causal cell types is likely key to uncoupling these disease processes and may identify novel therapeutic targets that replace the need for cell ablation.This Review explores the complex roles of immune cells in the onset and progression of multiple sclerosis, describing the influence of environmental and genetic factors on immune cell phenotype and function. The authors highlight that teasing out the precise roles of different immune cell subsets at different stages of the disease will be key to effective treatment strategies.

AB - Our incomplete understanding of the causes and pathways involved in the onset and progression of multiple sclerosis (MS) limits our ability to effectively treat this complex neurological disease. Recent studies explore the role of immune cells at different stages of MS and how they interact with cells of the central nervous system (CNS). The findings presented here begin to question the exclusivity of an antigen-specific cause and highlight how seemingly distinct immune cell types can share common functions that drive disease. Innovative techniques further expose new disease-associated immune cell populations and reinforce how environmental context is critical to their phenotype and subsequent role in disease. Importantly, the differentiation of immune cells into a pathogenic state is potentially reversible through therapeutic manipulation. As such, understanding the mechanisms that provide plasticity to causal cell types is likely key to uncoupling these disease processes and may identify novel therapeutic targets that replace the need for cell ablation.This Review explores the complex roles of immune cells in the onset and progression of multiple sclerosis, describing the influence of environmental and genetic factors on immune cell phenotype and function. The authors highlight that teasing out the precise roles of different immune cell subsets at different stages of the disease will be key to effective treatment strategies.

KW - CENTRAL-NERVOUS-SYSTEM

KW - CD8(+) T-CELLS

KW - PLASMACYTOID DENDRITIC CELLS

KW - INTERFERON-BETA THERAPY

KW - NATURAL-KILLER-CELLS

KW - CEREBROSPINAL-FLUID

KW - PERIPHERAL-BLOOD

KW - GENETIC RISK

KW - MAIT CELLS

KW - TH17 CELLS

U2 - 10.1038/s41577-022-00718-z

DO - 10.1038/s41577-022-00718-z

M3 - Review

C2 - 35508809

VL - 22

SP - 734

EP - 750

JO - Nature Reviews Immunology

JF - Nature Reviews Immunology

SN - 1474-1733

IS - 12

ER -