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Neuroimmune Mechanisms of Cerebellar Development and Its Developmental Disorders: Bidirectional Link Between the Immune System and Nervous System

  • Nour Eissa
  • Laëtitia Kermarrec
  • Jean-Eric GhiaEmail author
Part of the Contemporary Clinical Neuroscience book series (CCNE)

Abstract

Understanding the cross talk between the immune system and cerebellum development has noticeable implications for understanding and management of neurodevelopmental disorders. Our knowledge about cerebellar developmental maturation and remodeling is improving. Immune cells have different functions in a healthy state, but those functions are compromised during developmental stages in mammals. In this chapter, we highlight the evidence that indicates an important role of the immune system within the cerebellum and brain. We discuss the contribution of different immune responses in the development of the cerebellum and its associated disorders and highlight current understanding of the mechanisms and insights involved in these processes. Immune pathways that have a crucial role in cerebellar development are likely to become therapeutic targets for several neurodevelopmental disorders. Therefore, this information may suggest new therapeutic approaches to developmental disorders of the cerebellum through suppression or activation of selected immune pathways.

Keywords

Cerebellum Brain Innate immunity Adaptive immunity Cytokines Hypothalamic–pituitary–adrenal 

Abbreviations

AICA

Anterior inferior cerebellar artery

ALRs

AIM2-like receptors

ALS

Amyotrophic lateral sclerosis

ANS

Autonomic nervous system

APCs

Antigen-presenting cells

BBB

Blood–brain barrier

CCL

C-C motif chemokine ligand

CNS

Central nervous system

Cop-1

Copolymer 1

CSF

Cerebrospinal fluid

DAMPs

Damage-associated molecular patterns

DC

Dendritic cells

EAE

Experimental autoimmune encephalomyelitis

EGL

External granule cell layer

FOXP3

Forkhead box P3

GAD

Glutamic acid decarboxylase antibodies

GIT

Gastrointestinal tract

HE

Hashimoto’s encephalopathy

HSP

Heat shock proteins

IBS

Irritable bowel syndrome

IFN

Interferon

Ig

Immunoglobulin

IGL

Internal granule cell layer

IL

Interleukin

LGP2

Laboratory of genetics and physiology 2

MDA5

Melanoma differentiation-associated gene 5

MHC

Major histocompatibility

MIP

Macrophage inflammatory protein

MSA

Multiple system atrophy

NLRs

Nod-like receptors

OPCA

Olivopontocerebellar

P2X7R

Purinergic receptor P2X7

PACA

Primary autoimmune cerebellar ataxia

PAMPs

Pathogen-associated molecular patterns

PICA

Posterior inferior cerebellar artery

PRRs

Pattern recognition receptors

(RAG)-1

Recombination activating gene

Rig1

Retinoic acid-inducible gene-1

RLRs

RIG-like receptors

Rora

Retinoic acid-related orphan receptor alpha

ROS

Reactive oxygen species

SCA

Superior cerebellar artery

SCID

Severe combined immunodeficiency

SND

Striatonigral

SOCS3

Suppressor of cytokine signaling 3

TGF

Tumor growth factor

Th

T helper

TLRs

Toll-like receptors

TNF

Tumor necrosis factor

Treg

Regulatory T cells

URL

Upper rhombic lip

Notes

Funding

This was supported by grants from the Canadian Foundation for Innovation, Crohn’s and Colitis Canada, Research Manitoba, Children’s Hospital Research Institute of Manitoba, Canadian Institutes of Health Research to JEG, and University of Manitoba, Research Manitoba and Health Sciences Foundation – Mindel and Tom Olenick Research Award in Immunology to NE.

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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Nour Eissa
    • 1
    • 2
  • Laëtitia Kermarrec
    • 1
  • Jean-Eric Ghia
    • 1
    • 3
    • 4
    • 2
    • 5
    Email author
  1. 1.ImmunologyUniversity of ManitobaWinnipegCanada
  2. 2.Children’s Hospital Research Institute of ManitobaUniversity of ManitobaWinnipegCanada
  3. 3.Internal Medicine, Section of GastroenterologyUniversity of ManitobaWinnipegCanada
  4. 4.IBD Clinical and Research CentreUniversity of ManitobaWinnipegCanada
  5. 5.Department of Immunology, College of MedicineUniversity of ManitobaWinnipegCanada

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