Autism is a developmental neurological disorder that is still not really understood completely in spite of the large number of patients that are on the spectrum all over the world.
That being said, it is known that immune abnormalities, which are generally linked to many other diseases, also play a significant role in the development of autism and disturbances of the peripheral immune system as well as brain inflammation are often observed in those diagnosed with autism.
Immune abnormalities are also accompanied by intestinal microbiota abnormalities but the essential mechanisms responsible for these immune abnormalities have not been totally figured out for the longest time.
A research team that looked into the cause of autism focused on the hematopoietic cells which immune cells are derived from but also the aorta-gonad-mesonephros and the yolk sac, all involved in hematopoiesis in the fetus stage.
As part of the research, BTBR mice were used as a model for autism and the results sought a common ancestor of peripheral immune system abnormalities and inflation in the brain.
The origin of immune abnormalities was traced back to the embryonic stages of the yolk sac and aorta-gonad-mesonephros through the single cell RNA sequencing of the mice, identifying where peripheral immune cells and microglia are different.
Through HDAC1, the scientists also found a common mechanism of transcriptional regulation.
Furthermore, they showed that by manipulating epigenetic mechanisms in some specific developmental stages, immune abnormalities in the brain and peripheral tissues could be restored.
More precisely, HDAC1 was identified as a common mechanism.
Therefore, mice suppressed elevated inflammatory cytokines as well as microglial activation during the fetal stage thanks to administrating inhibitors of sodium butyrate or Romidepsin.
All in all, the study showed that abnormalities in the brain and peripheral organs, which are often seen in people on the spectrum are caused by epigenetic abnormalities in the hematopoietic stem cell lineage which is considered the ancestor of immune cells.
The study pretty much managed to find the missing piece that solved the autism puzzle, proving that the pathogenesis mechanism is an important step to solving the heterogeneity of the Autism Spectrum Disorder, which is great for developing new efficient treatments in the future.