Regulation of expression of “pancreatic” proteases in dendritic cells: a novel mechanism of peripheral tolerance (100.34)

TL;DRAbstract

Abstract MUC1 is a tumor-associated antigen. MUC1-specific TCR transgenic CD4+ T cells transferred into MUC1 Tg mice show less proliferation in response to vaccination with DC loaded with MUC1 peptide (DC/MUC1p) compared to WT. To query the underlying regulatory mechanisms, we vaccinated WT and Tg mice with DC/MUC1p and conducted transciptome analysis of splenic RNA. Proteases previously characterized as pancreas-restricted (Trypsin, Elastase and Carboxypeptidase B1) were significantly down-regulated in splenic DC from Tg mice relative to WT. Vaccination with soluble MUC1p gave the same result. Protease mRNA down-regulation in DC correlated with the reduction at the protein level. In related work we have shown that these enzymes are regulated by DC/T effector versus T reg interactions. Inhibition of Trypsin or CPB1 decreases the ability of DC to elicit MUC1-specific CD4 T cell response in vitro, supporting a correlation between deficient protease expression in DC and reduced T cell res

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