Possible pathogenic engagement of soluble Semaphorin 4D produced by γδT cells in medication-related osteonecrosis of the jaw (MRONJ).
Biochem Biophys Res Commun
; 480(1): 42-47, 2016 Nov 04.
Article
em En
| MEDLINE
| ID: mdl-27720716
ABSTRACT
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 γδT cells (90% of lymphocytes) express Semaphorin 4D (Sema4D) in human patient with MRONJ lesion, whereas γδT 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 γδT, but not αßT, cells infiltrating in the MRONJ-like lesion was observed. Both elevated soluble Sema4D (sSema4D) production accompanied by pro-inflammatory cytokines, including TNF-α IFN-γ and IL-1ß, and Sema4D-expressing γδT cells were detected in mouse MRONJ-like lesion. Activated γδT cells produced sSema4D in vitro, which could promote TNF-α production from macrophages. Meanwhile, γδT cell-KO mice were resistant to the induction of MRONJ and, hence, showed no elevation of local productions of Sema4D and TNF-α. Finally, systemic administration of anti-Sema4D neutralizing mAb suppressed the onset of MRONJ in wild-type mice in conjunction with diminished level of TNF-α. These results suggested a critical pathogenic engagement of Sema4D produced by γδT cells in the development of MRONJ.
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Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
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Antígenos CD
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Semaforinas
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Osteonecrose da Arcada Osseodentária Associada a Difosfonatos
Tipo de estudo:
Etiology_studies
Limite:
Animals
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Female
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Humans
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Middle aged
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article