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Novel Functions of RANK(L) Signaling in the Immune System

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Osteoimmunology

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 658))

Abstract

The TNF family members RANKL and its receptor RANK have initially been described as factors expressed on T cells and dendritic cells (DCs), respectively, and have been shown to augment the ability of DCs to stimulate naive T cell proliferation and enhance DC survival. Since another, yet soluble receptor for RANKL, namely OPG, was initially characterized as a factor inhibiting osteoclast development and bone resorption, it was somewhat enigmatic at first why one and the same genes would be essential both for the immune system and bone development – two processes that on first sight do not have much in common. However, in a series of experiments it was conclusively shown that RANKL-expressing T cells can also activate RANK-expressing osteoclasts, and thereby in principal mimicking RANKL-expressing osteoblasts. These findings lead to a paradigm shift and helped to coin the term osteoimmunology in order to account for the crosstalk of immune cells and bone. More importantly was that these findings also provided a rationale for the bone loss observed in patients with a chronically activated immune system such as in rheumatoid arthritis, leukemias, or the like, arguing that T cells, which were activated during the course of the disease to fight it off, also express RANKL, which induces osteoclastogenesis and thereby shifts the intricate balance of bone deposition and resorption in favor of the latter. Through knockout mice it became also clear that the RANKL-RANK-OPG system is involved in other processes such as in controlling autoimmunity or immune responses in the skin. We will briefly summarize the role of RANK(L) signaling in the immune system before we discuss some of the recent data we and others have obtained on the role of RANK(L) in controlling autoimmunity and immune responses in the skin.

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Abbreviations

TNF:

Tumor Necrosis Factor

RANKL:

Receptor Activator of Nuclear Factor-κB (NF-κB) Ligand

RANK:

Receptor Activator of Nuclear Factor-κB (NF-κB)

OPG:

Osteoprotegerin

DCs:

Dendritic Cells

LT:

Lymphotoxin

PPs:

Peyer’s Patches

LNs:

Lymph Nodes

ALPS:

Autoimmune Lymphoproliferative Syndrome

cTEC:

Cortical Thymic Epithelial Cell

mTEC:

Medullary Thymic Epithelial Cell

TRA:

Tissue Restricted Antigen

AIRE:

Autoimmune Regulator

LTi:

Lymphoid Tissue Inducer

Tregs:

eRgulatory T Cells

LCs:

Langerhans Cells

RA:

Rheumatoid Arthritis

BMD:

Bone Mineral Density

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  1. IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr-Gasse 3, A-1030, Vienna, Austria

    Andreas Leibbrandt & Josef M. Penninger

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  1. Andreas Leibbrandt
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  2. Josef M. Penninger
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Correspondence to Josef M. Penninger .

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  1. School of Medicine, University of Pennsylvania, Curie Blvd., Philadelphia, 19104, U.S.A.

    Yongwon Choi

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Leibbrandt, A., Penninger, J.M. (2009). Novel Functions of RANK(L) Signaling in the Immune System. In: Choi, Y. (eds) Osteoimmunology. Advances in Experimental Medicine and Biology, vol 658. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-1050-9_9

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