# Immune regulation and autism

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $392,500

## Abstract

Project Summary/Abstract: Many in vitro studies, post-mortem brain studies, and proteomic studies in
plasma and cerebral spinal fluid have described the presence of increased immune activation in ASD, whilst
clinical and epidemiological studies suggest that there is an increase in immune mediated conditions such as
atopy and autoimmunity. Activation of these immune responses is more prominent in individuals with
exacerbated behavioral impairments in ASD. Despite recent advances, there is a large gap in our knowledge
regarding pathophysiological pathways in ASD. We hypothesize that an underlying mechanism common to this
diverse array of findings is the lack of immune control or regulation that can lead to immune activation and
inflammation. Regulatory T cells (Tregs) are key mediators of immune tolerance that maintain their lineage
commitment and function through epigenetic regulation, and restrain inappropriate inflammation. We and
others have previously demonstrated decreased frequencies of Tregs-and immunosuppressive cytokines
including transforming growth factor (TGF)1 and interleukin (IL)-10.Our new preliminary data shows that
these immune regulatory deficits are associated with more severe behavioral phenotypes. However, no studies
have yet to address the functional cellular mechanisms of Tregs in ASD. We will test the innovative hypothesis
that a lack of cellular immune regulation is an early predictive risk factor for ASD, and that it endures in children
with ASD who have received a diagnosis. Considering that impairments in social interaction and anxiety are
key features of ASD, the amygdala has been extensively implicated in ASD pathophysiology. We will also
address the absence of immune regulation in the amygdala of individuals with ASD and matched controls over
development. This is an important area of investigation since therapeutic targeting of immune control
mechanisms might improve immune function, address abnormal amygdala development and alleviate
behavioral abnormalities. The proposed studies will determine immune regulation, Treg cellular function and
epigenetic mechanisms controlling Tregs commitment and stability (Aim #1) in children with ASD and typically
developing (TD) controls. In two prospective, population based cohorts we will examine immune regulatory
mechanisms in cord blood samples from children that later receive a diagnosis of ASD, or TD (Aim #2). The
proposal will directly assess the relationship of predictive and longitudinal measures of immune dysregulation
and behavior abnormalities in ASD. We will examine amygdala growth over development into adulthood and
immune regulation in human samples from ASD and TD controls (Aim #3). If successful, this research will
validate the transformative concept that ASD is, for some, a disorder due to defects in immune regulation and
will validate a novel mechanism for one of the most visible public health concerns of our time.
.

## Key facts

- **NIH application ID:** 9984551
- **Project number:** 5R01MH118209-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Paul Ashwood
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $392,500
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984551

## Citation

> US National Institutes of Health, RePORTER application 9984551, Immune regulation and autism (5R01MH118209-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9984551. Licensed CC0.

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