Associations between Monocyte and T Cell Cytokine Profiles in Autism Spectrum Disorders: Effects of Dysregulated Innate Immune Responses on Adaptive Responses to Recall Antigens in a Subset of ASD Children.

Harumi Jyonouchi,Lee Geng

doi:10.3390/ijms20194731

Abstract

Changes in monocyte cytokine production with toll like receptor (TLR) agonists in subjects with autism spectrum disorders (ASD) were best reflected by the IL-1β/IL-10 ratios in our previous research. The IL-1β/IL-10 based subgrouping (low, normal, and high) of ASD samples revealed marked differences in microRNA expression, and mitochondrial respiration. However, it is unknown whether the IL-1β/IL-10 ratio based subgrouping is associated with changes in T cell cytokine profiles or monocyte cytokine profiles with non-TLR agonists. In ASD (n = 152) and non-ASD (n = 41) subjects, cytokine production by peripheral blood monocytes (PBMo) with TLR agonists and β-glucan, an inflammasome agonist, and T cell cytokine production by peripheral blood mononuclear cells (PBMCs) with recall antigens (Ags) (food and candida Ags) were concurrently measured. Changes in monocyte cytokine profiles were observed with β-glucan in the IL-1β/IL-10 ratio based ASD subgroups, along with changes in T cell cytokine production and ASD subgroup-specific correlations between T cell and monocyte cytokine production. Non-ASD controls revealed considerably less of such correlations. Altered innate immune responses in a subset of ASD children are not restricted to TLR pathways and correlated with changes in T cell cytokine production. Altered trained immunity may play a role in the above described changes.

Highlights

Autism spectrum disorder (ASD) is a behaviorally defined syndrome and the effects of genetic and environmental factors that form its pathogenesis, likely vary in individuals with ASD diagnosis
non-IgE mediated food allergy (NFA) is thought to be associated with cellular immune reactivity to common food proteins, and we have previously reported that ASD children reveal increased T cell cytokine production (TNF-α, IFN-γ, and IL-12) against cow’s milk proteins at a high frequency
There are no statistical differences in gender frequency and clinical characteristics (ASD severity, cognitive development, sleep, GI symptoms, history of non-IgE mediated food allergy (NFA), seizure disorders, specific antibody deficiency, allergic rhinitis (AR), and asthma) by Chi-Square test (p > 0.05) (Table 1)

Summary

Introduction

Autism spectrum disorder (ASD) is a behaviorally defined syndrome and the effects of genetic and environmental factors that form its pathogenesis, likely vary in individuals with ASD diagnosis. One of the most extensively studied animal models of ASD is generated by inducing sterile inflammation in pregnant rodents through intraperitoneal injection of stimulants of innate immunity, such as endotoxin [4]. This model which is called maternal immune activation (MIA) has been shown to create lasting neurodevelopmental and behavioral changes in offspring, as well as lasting effects on T cell functions [4,5,6]. Our previous research indicated an association between fluctuating behavioral symptoms and dysregulated innate immune responses [9,10]

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