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Experimental models of spontaneous autoimmune disease in the central nervous system

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Abstract

Animal models have become essential tools for studying the human autoimmune disease. They are of vital importance in explorations of disease aspects, where, for diverse reasons, human material is unavailable. This is especially true for disease processes preceding clinical diagnosis and for tissues, which are inaccessible to routine biopsy. Early developing multiple sclerosis (MS) makes an excellent point in case for these limitations. Useful disease models should be developing spontaneously, without a need of artificial, adjuvant-supported induction protocols, and they should reflect credibly at least some of the complex features of human disease. The aim of this review is to compile models that exhibit spontaneous organ-specific autoimmunity and explore their use for studying MS. We first evaluate a few naturally occurring models of organ-specific autoimmune diseases and then screen autoimmunity in animals with compromised immune regulation (neonatal thymectomy, transgenesis, etc.). While most of these models affect organs other than the nervous tissues, central nervous system (CNS)-specific autoimmune disease is readily noted either after transgenic overexpression of cytokines or chemokines within the CNS or by introducing CNS-specific immune receptors into the lymphocyte repertoire. Most recently, spontaneous autoimmunity resembling MS was obtained by transgenic expression of self-reactive T cell receptors and B cell receptors. These transgenic models are not only of promise for studying directly disease processes during the entire course of the disease but may also be helpful in drug discovery.

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Abbreviations

Aire:

Autoimmune regulator

ALD:

Adrenoleukodystrophy

APECED:

Autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy

BBB:

Blood–brain barrier

CNS:

Central nervous system

CTLA-4:

Cytotoxic T-lymphocyte-associated protein 4

EAE:

Experimental autoimmune encephalomyelitis

GALC:

Galactosylceramidase

GITR:

Glucocorticoid-induced tumor necrosis factor receptor family-related gene

GFAP:

Glial fibrillary acidic protein

HA:

Hemagglutinin

ICOS:

Inducible T-cell costimulator

ICAM-1:

Intercellular adhesion molecule-1

Ig:

immunoglobulin

IL-2:

Interleukin-2

IFN-γ :

Interferon-γ

LPS:

Lipopolysaccharide

MBP:

Myelin basic protein

MHC:

Major histocompatibility complex

MOG:

Myelin oligodendrocyte glycoprotein

MS:

Multiple Sclerosis

NOD:

Nonobese diabetic

OS:

Obese strain

OSE:

Opticospinal encephalomyelitis

PLP:

Proteolipid protein

PNS:

Peripheral nervous system

PD-1:

Program death 1

RAG:

Recombinase-activating gene

SPF:

Specific pathogen-free

TCR:

T cell receptor

T1D:

Type 1 Diabetes mellitus

TLR:

Toll-like receptor

TNF-α :

Tumor necrosis factor-α

Treg:

Regulatory T cells

VCAM-1:

Vascular cell adhesion molecule-1

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Authors and Affiliations

  1. Department of Neuroimmunology, Max Planck Institute for Neurobiology, Am Klopferspitz 18, 82152, Martinsried, Germany

    Gurumoorthy Krishnamoorthy & Hartmut Wekerle

  2. Department of Cell and Molecular Biology, TU Braunschweig, Spielmannstrasse 7, 38106, Braunschweig, Germany

    Andreas Holz

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  1. Gurumoorthy Krishnamoorthy
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  2. Andreas Holz
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  3. Hartmut Wekerle
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Correspondence to Hartmut Wekerle.

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Krishnamoorthy, G., Holz, A. & Wekerle, H. Experimental models of spontaneous autoimmune disease in the central nervous system. J Mol Med 85, 1161–1173 (2007). https://doi.org/10.1007/s00109-007-0218-x

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  • DOI: https://doi.org/10.1007/s00109-007-0218-x

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