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

Conference paper
Part of the Advances in Experimental Medicine and Biology book series (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.

Keywords

RANK RANKL OPG Osteoimmunology Osteoclast Osteoclastogenesis Immune system Rheumatoid arthritis Osteoporosis Autoimmunity 

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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© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.IMBAInstitute of Molecular Biotechnology of the Austrian Academy of SciencesViennaAustria

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