| First Author | Li JY | Year | 2015 |
| Journal | Cell Metab | Volume | 22 |
| Issue | 5 | Pages | 799-810 |
| PubMed ID | 26456334 | Mgi Jnum | J:299572 |
| Mgi Id | MGI:6501239 | Doi | 10.1016/j.cmet.2015.09.012 |
| Citation | Li JY, et al. (2015) IL-17A Is Increased in Humans with Primary Hyperparathyroidism and Mediates PTH-Induced Bone Loss in Mice. Cell Metab 22(5):799-810 |
| abstractText | Primary hyperparathyroidism (PHPT) is a common cause of bone loss that is modeled by continuous PTH (cPTH) infusion. Here we show that the inflammatory cytokine IL-17A is upregulated by PHPT in humans and cPTH in mice. In humans, IL-17A is normalized by parathyroidectomy. In mice, treatment with anti-IL-17A antibody and silencing of IL-17A receptor IL-17RA prevent cPTH-induced osteocytic and osteoblastic RANKL production and bone loss. Mechanistically, cPTH stimulates conventional T cell production of TNFalpha (TNF), which increases the differentiation of IL-17A-producing Th17 cells via TNF receptor 1 (TNFR1) signaling in CD4(+) cells. Moreover, cPTH enhances the sensitivity of naive CD4(+) cells to TNF via GalphaS/cAMP/Ca(2+) signaling. Accordingly, conditional deletion of GalphaS in CD4(+) cells and treatment with the calcium channel blocker diltiazem prevents Th17 cell expansion and blocks cPTH-induced bone loss. Neutralization of IL-17A and calcium channel blockers may thus represent novel therapeutic strategies for hyperparathyroidism. |
