| First Author | Mizraji G | Year | 2017 |
| Journal | Cell Rep | Volume | 18 |
| Issue | 2 | Pages | 419-431 |
| PubMed ID | 28076786 | Mgi Jnum | J:251550 |
| Mgi Id | MGI:6103624 | Doi | 10.1016/j.celrep.2016.12.047 |
| Citation | Mizraji G, et al. (2017) Porphyromonas gingivalis Promotes Unrestrained Type I Interferon Production by Dysregulating TAM Signaling via MYD88 Degradation. Cell Rep 18(2):419-431 |
| abstractText | Whereas type I interferons (IFNs-I) were proposed to be elevated in human periodontitis, their role in the disease remains elusive. Using a bacterial-induced model of murine periodontitis, we revealed a prolonged elevation in IFN-I expression. This was due to the downregulation of TAM signaling, a major negative regulator of IFN-I. Further examination revealed that the expression of certain TAM components was reduced as a result of prolonged degradation of MYD88 by the infection. As a result of such prolonged IFN-I production, innate immunological functions of the gingiva were disrupted, and CD4(+) T cells were constitutively primed by dendritic cells, leading to elevated RANKL expression and, subsequently, alveolar bone loss (ABL). Blocking IFN-I signaling restored proper immunological function and prevented ABL. Importantly, a loss of negative regulation on IFN-I expression by TAM signaling was also evident in periodontitis patients. These findings thus suggest a role for IFN-I in the pathogenesis of periodontitis. |
