| First Author | Movila A | Year | 2016 |
| Journal | Biochem Biophys Res Commun | Volume | 480 |
| Issue | 1 | Pages | 42-47 |
| PubMed ID | 27720716 | Mgi Jnum | J:240726 |
| Mgi Id | MGI:5888978 | Doi | 10.1016/j.bbrc.2016.10.012 |
| Citation | Movila A, et al. (2016) Possible pathogenic engagement of soluble Semaphorin 4D produced by gammadeltaT cells in medication-related osteonecrosis of the jaw (MRONJ). Biochem Biophys Res Commun 480(1):42-47 |
| abstractText | Prior consensus held that medication-related osteonecrosis of the jaw (MRONJ) lesion was composed of necrotic bone; however, more recent studies have identified inflammatory infiltrates in the lesion. Herein, we report that remarkably elevated infiltrating gammadeltaT cells (90% of lymphocytes) express Semaphorin 4D (Sema4D) in human patient with MRONJ lesion, whereas gammadeltaT cells only account for 2-5% of lymphocytes in blood. Importantly, Sema4D is implicated in the pathogenesis of T cell-mediated inflammatory diseases, such as rheumatoid arthritis and multiple sclerosis. Indeed, in a mouse model of MRONJ, an elevated number of gammadeltaT, but not alphabetaT, cells infiltrating in the MRONJ-like lesion was observed. Both elevated soluble Sema4D (sSema4D) production accompanied by pro-inflammatory cytokines, including TNF-alpha IFN-gamma and IL-1beta, and Sema4D-expressing gammadeltaT cells were detected in mouse MRONJ-like lesion. Activated gammadeltaT cells produced sSema4D in vitro, which could promote TNF-alpha production from macrophages. Meanwhile, gammadeltaT cell-KO mice were resistant to the induction of MRONJ and, hence, showed no elevation of local productions of Sema4D and TNF-alpha. Finally, systemic administration of anti-Sema4D neutralizing mAb suppressed the onset of MRONJ in wild-type mice in conjunction with diminished level of TNF-alpha. These results suggested a critical pathogenic engagement of Sema4D produced by gammadeltaT cells in the development of MRONJ. |
