Gadd45 Proteins in Immunity

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


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.


Experimental Autoimmune Encephalomyelitis Adaptive Immune System Gadd45 Protein Tyr323Phe Mutation Gadd45 Gene Expression 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.





B cell lymphoma x large


Cellular FLICE inhibitory protein


Casitas B-lineage lymphoma proto-oncogene b


Cluster of differentiation


Cluster of differentiation 4-positive


Cluster of differentiation 8-positive


C-type lectin receptor


Cytokine response gene 6


Death-inducing signalling complex


Experimental autoimmune encephalomyelitis


Early growth response


Granulocyte colony-stimulating factor


Growth arrest and DNA damage 45


Granulocyte–macrophage colony-stimulating factor


Gene related to anergy in lymphocytes protein






c-Jun N-terminal kinase




Macrophage colony-stimulating factor


Mitogen-activated protein kinase


MAPK/ERK kinase kinase 4


Major histocompatibility complex


Mitogen-activated protein kinase kinase


Myelin oligodendrocyte glycoprotein


Myeloid differentiation primary response protein 118


Nuclear factor of activated T cells


Nuclear factor κB


Natural killer T cell


Nod-like receptor


Pathogen-associated molecular pattern


Pattern recognition receptor


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


Reactive oxygen species


Signal transducer and activator of transcription


T cell receptor


Transforming growth factor beta


T helper


Toll-like receptor


Tumour necrosis factor alpha


Tumour necrosis factor receptor 1


Viral mitochondrial-localized inhibitor of apoptosis


Zeta-chain associated protein of 70 kDa



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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© 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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