E3 Ubiquitin Ligase Von Hippel-Lindau Protein Promotes Th17 Differentiation.

Von Hippel-Lindau (VHL) is an E3 ubiquitin ligase that targets proteins, including HIF-1α, for proteasomal degradation. VHL and HIF regulate the balance between glycolysis and oxidative phosphorylation, which is critical in highly dynamic T cells. HIF-1α positively regulates Th17 differentiation, a complex process in which quiescent naive CD4 T cells undergo transcriptional changes to effector cells, which are commonly dysregulated in autoimmune diseases.

IL-22 deficiency increases CD4 T cell responses to mucosal immunization.

Mucosal vaccines are a promising platform for combatting infectious diseases for which we still lack effective preventative measures. Optimizing these vaccines to generate the best protective immune responses with the least complicated immunization regimen is imperative. Mucosal barriers are the first line of defense against many pathogens and, as such, we looked to their biology for strategies to improve vaccine delivery.

Hypoxic modulation of hepatocyte responses to the cytokine interleukin-22.

The cytokine interleukin-22 (IL-22) is a potent regulator of tissue responses during inflammation. Depending on the context of inflammation, IL-22 can have protective or inflammatory effects on epithelial cells. This dual nature of IL-22 leads us to hypothesize that its activity must be exquisitely regulated to prevent host tissue damage.

Transcription Factor HIF-1α Controls Expression of the Cytokine IL-22 in CD4 T Cells.

IL-22 is expressed by activated lymphocytes and is important in modulation of tissue responses during inflammation. The cytokine induces proliferative and antiapoptotic pathways in epithelial cells allowing enhanced cell survival. This can have positive effects, such as in the maintenance of epithelial barriers in the gastrointestinal tract, but also negative effects, such as contributing to colorectal tumorigenesis.