A recent study published in the latest issue of the Journal
Science (January 29th 2016) emphasized the key role of
maternal inflammation during pregnancy, that disrupts fetal brain development and could lead to
Previous study in mice showed that the induction of inflammation during
pregnancy, with a viral infection that triggers maternal immune activation
(MIA), affects fetal brain development with dramatic consequences on pups
that develop autism-like behavioral abnormalities (1-3).
The present study goes a step further by identifying immune cells whose
secretion directly impact fetal brain formation,
Th17 cells and clearly demonstrated thatblocking IL17 pathway could prevent autism-like behavior in the offspring.
1- Th17 cells and IL17a production in Autism
T helper 17 (Th17) cells are involved in immune responses against bacteria.
Via the production of pro-inflammatory cytokines, with interleukin -17a
(IL-17a) being the predominant Th17 cytokine, these cells play a central
role in inflammatory and autoimmune diseases including but not limited
to asthma, rheumatoid arthritis, psoriasis, inflammatory bowel disease
(IBD) and multiple sclerosis (4).
a- What is known about IL-17 in relation to Autism?
IL-17a was found in the serum of a subset of autistic children (5-6).
A recent study has also shown that higher levels of IL-17 were detected
in the serum of autistic children when compared to healthy controls and
these levels were even higher when the autistic children were affected
by asthma too (7). In addition, genome-wide copy number variant (CNV)
analysis identified IL17a as one of many genes enriched in autistic patients (8).
Animal studies have similarly shown (MIA mouse model) that affected offspring
produced higher levels of IL-17a (9-10). Although IL-17a was shown as
a potential factor involved in autism development, studies did not focus
on showing what were the specific immune cell population involved.
b- What does this new study bring?
The authors of the current study created a mice model lacking a specific
factor, namely retinoic acid receptor–related orphan nuclear receptor
γt (RORγt KO mice model), crucial for the Th17 cells differentiation. These knock
out mice would not express Th17 cells, therefore they won’t be able
to synthesize IL-17a.
They showed that despite inducing maternal inflammation in pregnant mice,
the pregnant KO mothers
failed to produce IL-17a and their offspring had a
totally normal brain development with no autism-like behavioral abnormalities.
On the other hand, infected wild type pregnant mice (WT) developed an acute
immune response with high levels of IL-6, IL-17 and other pro-inflammatory
factors such as TNF-α.
High IL-17 levels were detected in the placenta and the decidual tissue
and IL-17 receptors expression (IL-17R) was strongly augmented in the
This led to:
- Abnormal cortical development in the offspring
- ASD-like behavioral abnormalities in the offspring
Interestingly, when the IL17/IL17R pathway was blocked using IL-17a blocking
antibody before the induced infection in the pregnant mice, the offspring
did not express higher levels of IL-17R and had
a normal brain development and no autistic behaviors.
Altogether, these data clearly pinpoint the key role of high IL-17 levels
as a cause for ASD development.
Most importantly, the study suggest that
Autism is preventable by inhibiting IL-17/IL17R pathway either by blocking IL17a production or action.
2- Th17 cells and IL-17a in Reccurent Pregnant Losses (RPL) or pregnancy
Some T cells can trigger an inflammatory response to fetal antigens leading
to miscarriages or pregnancy complications. Among others, Th17 cells producing
the inflammatory IL-17 have been reported to play a role in RPL.
A recent study conducted on 60 idiopathic RPL cases and 40 age-matched
fertile controls showed higher serum levels in RPL patients when compared
to controls (11). Another set of data confirmed these results and showed
that IL17 serum levels were even higher in obese RPL patients when compared
to lean RPL patients or fertile controls (12). Further, recent studies
attributed a role of Th17 and IL-17 in pre-eclampsia (13)
Interestingly, the pro-inflammatory effector cytokine IL-6, a key factor
for TH17 cell differentiation (14) was reported to be also highly expressed
in RPL patients when compared to controls (15) and high levels have been
correlated with severe case of pre-eclampsia (16).
Because, maternal inflammation is a risk factor for pregnancy loss, pregnancy
complications such as pre-eclampsia and could potentially disrupt fetal
brain development thus leading to Autism, it is
crucial to detect, treat and reduce any maternal immune alterations potentially deleterious to pregnancy maintenance and fetal health.
detecting and counteracting any increase in IL-17 producing cells, with appropriate immune therapy, we, at
Braverman Reproductive Immunology, strongly believe that we can help you to minimize your risk of having
a baby affected with Autism.