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Regulation of T cell-associated tissues and T cell activation by RANKL-RANK-OPG

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Abstract

The receptor activator of nuclear factor kappa-B ligand (RANKL)-RANK-osteoprotegerin (OPG) system is critical to bone homeostasis, but genetically deficient mouse models have revealed important roles in the immune system as well. RANKL-RANK-OPG is particularly important to T cell biology because of its organogenic control of thymic development and secondary lymphoid tissues influence central T cell tolerance and peripheral T cell function. RANKL-RANK-OPG cytokine-receptor interactions are often controlled by regulation of expression of RANKL on developing T cells, which interacts with RANK expressed on some lymphoid tissue cells to stimulate key downstream signaling pathways that affect critical tuning functions of the T cell compartment, like cell survival and antigen presentation. Activation of peripheral T cells is regulated by RANKL-enhanced dendritic cell survival, and dysregulation of the RANKL-RANK-OPG system in this context is associated with loss of T cell tolerance and autoimmune disease. Given its broader implications for immune homeostasis and osteoimmunology, it is critical to further understand how the RANKL-RANK-OPG system operates in T cell biology.

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Acknowledgements

The authors acknowledge grant support in part from the NIH (AR069546, AI125284, AR077526).

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This work was supported in part by grant support from the National Institutes of Health (NIH) (AR069546, AI125284, AR077526).

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  1. Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA

    Matthew C. Walsh & Yongwon Choi

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Walsh, M.C., Choi, Y. Regulation of T cell-associated tissues and T cell activation by RANKL-RANK-OPG. J Bone Miner Metab 39, 54–63 (2021). https://doi.org/10.1007/s00774-020-01178-y

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