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01.12.2017 | Research | Ausgabe 1/2017 Open Access

Journal of Neuroinflammation 1/2017

MicroRNA expression changes in association with changes in interleukin-1ß/interleukin10 ratios produced by monocytes in autism spectrum disorders: their association with neuropsychiatric symptoms and comorbid conditions (observational study)

Zeitschrift:
Journal of Neuroinflammation > Ausgabe 1/2017
Autoren:
Harumi Jyonouchi, Lee Geng, Deanna L. Streck, James J. Dermody, Gokce A. Toruner
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1186/​s12974-017-1003-6) contains supplementary material, which is available to authorized users.

Abstract

Background

MicroRNAs (miRNAs) play a major role in regulating immune responses at post-transcriptional levels. Previously, we have reported fluctuating interlukine-1ß (IL-1ß)/IL-10 ratios produced by peripheral blood monocytes (PBMo) in some patients with autism spectrum disorders (ASD). This study examined whether changes in miRNA expression by PBMo are associated with changes in IL-1ß/IL-10 ratios and how such changes are associated with ASD clinical features.

Methods

miRNA expression by purified PBMo from ASD subjects (N = 69) and non-ASD controls (N = 27) were determined by high-throughput sequencing. Cytokine production by PBMo in responses to stimuli of innate immunity, and behavioral symptoms [assessed by aberrant behavioral checklist (ABC)] were also evaluated at the same time of sample obtainment.

Results

As a whole, there was no difference in miRNA expression between ASD and control non-ASD PBMo. However, when ASD cells were subdivided into 3 groups with high, normal, or low IL-1ß/IL-10 ratios as defined in the “Results” section, in comparison with the data obtained from non-ASD controls, we observed marked changes in miRNA expression. Namely, over 3-fold changes in expression of miR-181a, miR-93, miR-223, miR-342, and miR-1248 were observed in ASD PBMo with high or low IL-1ß/IL-10 ratios, but not in ASD PBMo with normal ratios. These miRNAs that had altered in expression are those closely associated with the regulation of key signaling pathways. With changes in IL-1ß/IL-10 ratios, we also observed changes in the production of cytokines (IL-6, TNF-α, and TGF-ß) other than IL-1ß/IL-10 by ASD PBMo. The association between behavioral symptoms and cytokine levels was different when ASD cells exhibit high/low IL-1ß/IL-10 ratios vs. when ASD cells exhibited normal ratios. Non-IgE-mediated food allergy was also observed at higher frequency in ASD subjects with high/low IL-1ß/IL-10 ratios than with normal ratios.

Conclusions

Changes in cytokine profiles and miRNA expression by PBMo appear to be associated with changes in ASD behavioral symptoms. miRNAs that are altered in expression in ASD PBMo with high/low IL-1ß/IL-10 ratios are those associated with inflammatory responses. Changes in IL-1ß/IL-10 ratios along with changes in miRNA expression may serve as biomarkers for immune-mediated inflammation in ASD.
Zusatzmaterial
Additional file 2: Results of Z test of miRNA expression among ASD groups and non-ASD controls cells. (XLSX 182 kb)
12974_2017_1003_MOESM2_ESM.xlsx
Additional file 3: Results of Z test of miRNA expression between whole ASD cells and non-ASD control cells. (XLSX 261 kb)
12974_2017_1003_MOESM3_ESM.xlsx
Additional file 4: Results of miRNA target gene analysis of group A. (XLSX 626 kb)
12974_2017_1003_MOESM4_ESM.xlsx
Additional file 5: Results of miRNA target gene analysis of group B. (XLSX 543 kb)
12974_2017_1003_MOESM5_ESM.xlsx
Additional file 6: Results of miRNA target gene analysis of group C. (XLSX 105 kb)
12974_2017_1003_MOESM6_ESM.xlsx
Literatur
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