Gadd45 Proteins in Immunity

Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 793)

Abstract

The vertebrate immune system protects the host against invading pathogens such as viruses, bacteria and parasites. It consists of an innate branch and an adaptive branch that provide immediate and long-lasting protection, respectively. As the immune system is composed of different cell types and distributed throughout the whole body, immune cells need to communicate with each other. Intercellular communication in the immune system is mediated by cytokines, which bind to specific receptors on the cell surface and activate intracellular signalling networks. Growth arrest and DNA damage-inducible 45 (Gadd45) proteins are important components of these intracellular signalling networks. They are induced by a number of cytokines and by bacterial lipopolysaccharide. Within the innate immune system, Gadd45 proteins are crucial for the differentiation of myeloid cells as well as for the function of granulocytes and macrophages. Moreover, Gadd45β regulates autophagy, a catabolic pathway that also degrades intracellular pathogens. Regarding adaptive immunity, Gadd45 proteins are especially well characterized in T cells. For instance, Gadd45β and Gadd45γ regulate cytokine expression and Th1 differentiation, while Gadd45α inhibits p38 kinase activation downstream of the T cell receptor. Due to their many functions in the immune system, deficiency in Gadd45 proteins causes autoimmune diseases and less efficient tumour immunosurveillance.

Keywords

Arthritis Tyrosine Serine Interferon Dexamethasone 

Abbreviations

ATG

Autophagy-related

Bcl-xL

B cell lymphoma x large

c-FLIP

Cellular FLICE inhibitory protein

Cbl-b

Casitas B-lineage lymphoma proto-oncogene b

CD

Cluster of differentiation

CD4+

Cluster of differentiation 4-positive

CD8+

Cluster of differentiation 8-positive

CLR

C-type lectin receptor

CR6

Cytokine response gene 6

DISC

Death-inducing signalling complex

EAE

Experimental autoimmune encephalomyelitis

Egr

Early growth response

G-CSF

Granulocyte colony-stimulating factor

Gadd45

Growth arrest and DNA damage 45

GM-CSF

Granulocyte–macrophage colony-stimulating factor

GRAIL

Gene related to anergy in lymphocytes protein

IFN

Interferon

IL

Interleukin

JNK

c-Jun N-terminal kinase

LPS

Lipopolysaccharide

M-CSF

Macrophage colony-stimulating factor

MAPK

Mitogen-activated protein kinase

MEKK4

MAPK/ERK kinase kinase 4

MHC

Major histocompatibility complex

MKK

Mitogen-activated protein kinase kinase

MOG

Myelin oligodendrocyte glycoprotein

Myd118

Myeloid differentiation primary response protein 118

NFAT

Nuclear factor of activated T cells

NF-κB

Nuclear factor κB

NKT

Natural killer T cell

NLR

Nod-like receptor

PAMP

Pathogen-associated molecular pattern

PRR

Pattern recognition receptor

RLR

Retinoic acid-inducible gene (RIG)-I-like receptor

ROS

Reactive oxygen species

STAT

Signal transducer and activator of transcription

TCR

T cell receptor

TGF-β

Transforming growth factor beta

Th

T helper

TLR

Toll-like receptor

TNFα

Tumour necrosis factor alpha

TNFR1

Tumour necrosis factor receptor 1

vMIA

Viral mitochondrial-localized inhibitor of apoptosis

ZAP-70

Zeta-chain associated protein of 70 kDa

Notes

Acknowledgements

I am grateful to Dr. Yvonne Rauter and Alisha Walker for critically reading the manuscript and for helping with the figures. This work was supported by grants of the Deutsche Forschungsgemeinschaft (SCHM1586/3-1) and the Helmholtz Association cross-programme activity “Metabolic Dysfunction and Human Disease”.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Systems-Oriented Immunology and Inflammation ResearchHelmholtz Center for Infection ResearchBraunschweigGermany

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