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Molecular Mechanisms of Notch Signaling in Lymphoid Cell Lineages Development: NF-κB and Beyond

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Notch Signaling in Embryology and Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1227))

Abstract

Notch is a ligand–receptor interaction-triggered signaling cascade highly conserved, that influences multiple lineage decisions within the hematopoietic and the immune system. It is a recognized model of intercellular communication that plays an essential role in embryonic as well as in adult immune cell development and homeostasis. Four members belong to the family of Notch receptors (Notch1–4), and each of them plays nonredundant functions at several developmental stages. Canonical and noncanonical pathways of Notch signaling are multifaceted drivers of immune cells biology. In fact, increasing evidence highlighted Notch as an important modulator of immune responses, also in cancer microenvironment. In these contexts, multiple transduction signals, including canonical and alternative NF-κB pathways, play a relevant role. In this chapter, we will first describe the critical role of Notch and NF-κB signals in lymphoid lineages developing in thymus: natural killer T cells, thymocytes, and thymic T regulatory cells. We will address also the role played by ligand expressing cells. Given the importance of Notch/NF-κB cross talk, its role in T-cell leukemia development and progression will be discussed.

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Abbreviations

ANK:

Ankyrin domain

DSL:

Delta-Serrate

IKK:

Inhibitor of KAPPA-B kinase complex

Jagged:

Jag

N1ICD:

Notch1 intracellular domain

N2ICD:

Notch2 intracellular domain

N3ICD:

Notch3 intracellular domain

NF-κB:

Nuclear Factor-κB

NKT:

Natural Killer T cells

PEST:

Proline (P), glutamic acid (E), serine (S), and threonine (T)-rich protein

PTCRa:

Invariant pre-Talpha chain of the pre-TCR receptor

T-ALL:

T-cell acute lymphoblastic leukemia

Tregs:

T regulatory cells

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Acknowledgments

We thank members of Screpanti’s laboratory, whose comments and work have contributed to the realization of this chapter. Work in the author’s laboratories is supported by Grants from Italian Ministry of University and Research (MIUR), Sapienza University of Rome, and by Italian Ministry of Education, University and Research-Dipartimenti di Eccellenza-L.323/2016. This chapter is dedicated to the memory of Professor Alberto Gulino.

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Authors and Affiliations

  1. Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy

    G. Tsaouli & I. Screpanti

  2. Department of Immunology, Institute of Immunity and Transplantation, Royal Free Hospital, London, UK

    A. Barbarulo

  3. Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy

    A. Vacca & M. P. Felli

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  1. G. Tsaouli
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  2. A. Barbarulo
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  3. A. Vacca
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  4. I. Screpanti
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  5. M. P. Felli
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Correspondence to I. Screpanti or M. P. Felli .

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Editors and Affiliations

  1. Department of Dermatology, The Saarland University Hospital, Homburg, Saarland, Germany

    Jörg Reichrath

  2. Department of Dermatology, The Saarland University Hospital, Homburg, Saarland, Germany

    Sandra Reichrath

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Tsaouli, G., Barbarulo, A., Vacca, A., Screpanti, I., Felli, M.P. (2020). Molecular Mechanisms of Notch Signaling in Lymphoid Cell Lineages Development: NF-κB and Beyond. In: Reichrath, J., Reichrath, S. (eds) Notch Signaling in Embryology and Cancer. Advances in Experimental Medicine and Biology, vol 1227. Springer, Cham. https://doi.org/10.1007/978-3-030-36422-9_10

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