(bubbly music)
- [Narrator] Type 1 diabetes
involves pancreatic beta cells
being destroyed by the immune system.
However, until recently it wasn't clear
why the immune apparatus is activated
and directed against these cells.
Our recent research has
led to the discovery
that pancreatic beta cells
undergo premature senescence
during the early in the
development of type 1 diabetes.
These senescent beta cells
become pro-inflammatory.
They have the ability to induce senescence
in neighboring cells and also
initiate immune surveillance.
A variety of stress can lead to DNA damage
and to activation of two
cycling dependent kinases,
P16 and P21, stopping the cell cycle.
In these cells, where the
cell cycle is arrested,
chromatin reorganization
promotes the secretion
of a variety of factors.
This cell state is generally referred to
as senescence-associated
secretory phenotype, SASP.
The hallmarks of SASP include the ability
to induce SASP in neighboring cells,
release factors involved in
extracellular remodeling,
and recruit innate immune cells.
We have identified a key
chromatin regulator, BRD4,
that is necessary for the transition
of beta cells into a
pro-inflammatory state.
Inhibition of BRD4 limits the ability
of pro-inflammatory beta cells
to induce paracrine senescence
and recruit innate immune cells.
We have shown that in mice,
treatments that involve inhibition of BRD4
prevents the development
of type 1 diabetes.
We propose a new paradigm involving
accumulation of senescent beta cells,
leading to the development
of type 1 diabetes.
Understanding the interactions
of pro-inflammatory senescent
cells with immune surveillance
can lead to new drug
therapies for type 1 diabetes.
