Humoral immune responses are tailored to the invading pathogen through regulation of key transcription factors and their networks. This is critical to establishing effective antibody-mediated responses, yet it is unknown how B cells integrate pathogen-induced signals to drive or suppress transcriptional programs specialized for each class of pathogen. Here, we detail the key role of the transcription factor c-Myb in regulating the T-bet-mediated anti-viral program. Deletion of c-Myb in mature B cells significantly increased serum IgG2c and CXCR3 expression by upregulating T-bet, normally suppressed during Th2-cell-mediated responses. Enhanced expression of T-bet resulted in aberrant plasma cell differentiation within the germinal center, mediated by CXCR3 expression. These findings identify a dual role for c-Myb in limiting inappropriate effector responses while coordinating plasma cell differentiation with germinal center egress. Identifying such intrinsic regulators of specialized antibody responses can assist in vaccine design and therapeutic intervention in B-cell-mediated immune disorders.
Background Matrix metalloproteinases (MMPs) play a crucial role in the malignant phenotype of cancer cells. In particular, active levels of MMP2 in cancer cells have been associated with invasion and metastasis through the degradation of basement membrane extracellular matrix proteins. However, little is known about the role of this potential biomarker in oral cancer. Our aim was to investigate the effect of MMP2 inhibition on OSCC activity in vitro, as well as to assess MMP2 dysregulation in oral cancer samples. Methods Human OSCC cell lines H357 and H400 were tested with the selective MMP2 inhibitor ARP101 and the MMP2 neutralising monoclonal antibody MA5‐13590 to assess cell proliferation in vitro using MTS assay. Cell migration at 12/24 h was assessed using a Transwell migration assay. Cell invasion was assessed at 24 h using a Corning Matrigel invasion assay. MMP2 expression was assessed in 208 tissue samples (related to 60 OSCC cases and nine normal control) using tissue microarray (TMA) and further analysed via TCGA. Results Both ARP101 and MA5‐13590 monoclonal antibody reduced cell proliferation in both the cell lines tested. Treatment with 4μg/mL of MMP2 monoclonal antibody showed a significant decrease in cell migration at 24 hours. The administration of ARP101 and monoclonal antibody to H357 and H400 cell lines induced a drastic reduction in cell invasion at 24 h compared to the control. In patients, TCGA analysis demonstrated that oral cancer tissues express significantly higher levels of MMP2 mRNA compared to normal oral tissues. Further, IHC analysis on TMA showed significant difference in MMP2 protein expression between low and high histopathological grade OSCC. Conclusions We have demonstrated, for the first time, that MMP2 inhibition affects oral cancer cells ability to survive, migrate and invade in vitro. Differences between MMP2 expression in normal and malignant tissues varied. Further research on the role of MMP2 in OSCC and novel mechanisms to inhibit MMP2‐dependent pathways should be encouraged.
Objectives: To analyse the effectiveness of targeted stakeholder engagement strategies and the impact they have on antenatal referrals, oral health admission, attendance and education of pregnant women in a rural public dental clinic.Method: Key stakeholders (obstetric trained general practitioners [GPs] and midwives) were educated and motivated to refer pregnant women to the rural public dental clinic via priority referral pathways. A 10-month pre-and postintervention period of oral health assessments and treatments was compared and contrasted.Design: Quasi-experimental study. Setting: A rural health service in the Loddon Mallee region, Victoria. Participants: Local pregnant women, 18 years of age or older, eligible for public dental care. Main outcome measures: Increased oral health admission, attendance and education of pregnant women. Results: Active engagement with key stakeholders significantly increased the oral health referral, admission and attendance of eligible antenatal women. Prior to the intervention, only 15.04% of eligible antenatal women sought oral health treatment, in comparison with 40.37% post-intervention. Of the 62 women referred, 44 actively received dental care. Conclusion: Active engagement with key stakeholders has demonstrated a clinically effective method of increasing antenatal referrals of socially disadvantaged women to a rural public dental clinic. Further collaboration between healthcare professionals can improve the oral health admission rates, attendance and education of antenatal women and their children.
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