Abstract
Osteoimmunology is field of research dedicated to the study of the interactions between the immune system and bone. Among the cells of the immune system that regulate the skeleton in health and disease are T lymphocytes, T cells secrete inflammatory/osteoclastogenic cytokines such as RANKL, TNF, and IL-17, as well as factors that stimulate bone formation, including Wnt ligands. In addition, T cells regulate the differentiation and life span of stromal cells via CD40L and other costimulatory molecules expressed on their surface. Consensus exists that parathyroid hormone (PTH) induces bone loss by increasing the production of RANKL by osteocytes and osteoblast. However, new evidence suggests that PTH expands Th17 cells and increases IL-17 levels in mice and humans. Studies in the mouse of further shown that Th17 cell produced IL-17 acts as an “upstream cytokine” that increases the sensitivity of osteoblasts and osteocytes to PTH. As a result, PTH stimulates osteocytic and osteoblastic release of RANKL. Therefore, PTH cause bone loss only in the presence of IL-17 signaling. This article reviews the evidence that the effects of PTH are mediated not only by osteoblasts and osteocytes, but also T cells and IL-17.
Highlights
Parathyroid hormone (PTH) is an important regulator of calcium and phosphorus concentrations in extracellular fluid
Signaling events downstream of GαS include cAMP generation [49] and activation of L-type calcium channels [51], which promote Th1 and Th17 cell differentiation [50]. This evidence suggests the possibility that treatment with the L-type calcium channel blocker diltiazem may blunt the differentiation of CD4+ cells into Th17 cells [50] and prevent the bone loss induced by continuous PTH (cPTH). This hypothesis was tested in murine studies that revealed that diltiazem blocks the expansion of Th17 cells, the increase in bone resorption, and the loss of cortical and trabecular bone induced by cPTH
An impressive amount of work published in the last 10 years has led to the recognition that T cells play an unexpected role in the regulation of bone resorption and bone formation through a variety of mechanisms and the involvement of specialized cell lineages such as Th17 cells and Tregs
Summary
Received: 20 November 2015 Accepted: 05 February 2016 Published: 17 February 2016. Citation: Pacifici R (2016) The Role of IL-17 and TH17 Cells in the Bone Catabolic. Among the cells of the immune system that regulate the skeleton in health and disease are T lymphocytes, T cells secrete inflammatory/osteoclastogenic cytokines such as RANKL, TNF, and IL-17, as well as factors that stimulate bone formation, including Wnt ligands. Consensus exists that parathyroid hormone (PTH) induces bone loss by increasing the production of RANKL by osteocytes and osteoblast. New evidence suggests that PTH expands Th17 cells and increases IL-17 levels in mice and humans. Studies in the mouse of further shown that Th17 cell produced IL-17 acts as an “upstream cytokine” that increases the sensitivity of osteoblasts and osteocytes to PTH. PTH stimulates osteocytic and osteoblastic release of RANKL. This article reviews the evidence that the effects of PTH are mediated by osteoblasts and osteocytes, and T cells and IL-17
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