PMID: 20647758Jul 22, 2010Paper

In vivo depletion of T lymphocyte-specific transcription factors by RNA interference

Cell Cycle
Antoine TesniereGuido Kroemer

Abstract

The generation of specific T lymphocyte subsets is under the strict control of specific transcription factors, as this has been shown by knockout experiments in mice. Here, we show that siRNAs that specifically target the transcription factor Gata3 (which is required for the development of T helper 1 cells) or T-Bet (which is required for the development of T helper 2 cells) can be effective in vivo. Thus, the intraperitoneal injection of siRNAs specific for Gata3 or t-Bet leads to the specific depletion of their target gene products in vivo, in the spleen and in the lymph nodes of mice. The immunomodulatory action of these siRNAs was validated in a model of anti-tumor vaccination in which colorectal cancer cells that succumb to anthracyclin-induced immunogenic cell death were injected subcutaneously into one flank, in the absence of any adjuvant and live tumor cells were injected simultaneously in the opposite flank of immunocompetent mice. In this setting, the siRNA targeting t-Bet was able to accelerate tumor growth while the siRNA targeting Gata3 significantly reduced the proliferation of cancer cells in vivo. These effects were dependent on the immune response elicited by dying tumor cells because both siRNAs failed to mod...Continue Reading

Citations

Dec 22, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Garrett R Rettig, Mark A Behlke
Aug 23, 2011·Journal of Translational Medicine·Christoph BergmannGötz F Lehnerdt
Jun 13, 2016·International Journal of Hematology·Evidio Domingo-Musibay, Masato Yamamoto

❮ Previous
Next ❯

Related Concepts

Related Feeds

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms