Modulation of human endogenous retroviruses and cytokines expression in peripheral blood mononuclear cells from autistic children and their parents.
Antiretrovirals
Autism spectrum disorder
Biomarker
Cytokines
Gene expression
HEMO
HERVs
In vitro treatment
Mother–child association
Journal
Retrovirology
ISSN: 1742-4690
Titre abrégé: Retrovirology
Pays: England
ID NLM: 101216893
Informations de publication
Date de publication:
30 11 2022
30 11 2022
Historique:
received:
16
02
2022
accepted:
09
05
2022
entrez:
1
12
2022
pubmed:
2
12
2022
medline:
3
12
2022
Statut:
epublish
Résumé
Putative pathogenic effects mediated by human endogenous retroviruses (HERVs) in neurological and psychiatric disorders in humans have been extensively described. HERVs may alter the development of the brain by means of several mechanisms, including modulation of gene expression, alteration of DNA stability, and activation of immune system. We recently demonstrated that autistic children and their mothers share high expression levels of some HERVs and cytokines in peripheral blood mononuclear cells (PBMCs) ex vivo, suggesting a close mother-child association in Autism Spectrum Disorder (ASD). In the present study, PBMCs from autistic children and their parents were exposed to stimulating factors (Interleukin-2/Phytohaemagglutinin) or drugs, as Valproic acid and Efavirenz. The results show that HERVs and cytokines expression can be modulated in vitro by different stimuli in PBMCs from autistic children and their mothers, while no significant changes were found in PBMCs ASD fathers or in controls individuals. In particular, in vitro exposure to interleukin-2/Phytohaemagglutinin or valproic acid induces the expression of several HERVs and cytokines while Efavirenz inhibits them. Herein we show that autistic children and their mothers share an intrinsic responsiveness to in vitro microenvironmental changes in expressing HERVs and pro-inflammatory cytokines. Remarkably, the antiretroviral drug Efavirenz restores the expression of specific HERV families to values similar to those of the controls, also reducing the expression of proinflammatory cytokines but keeping the regulatory ones high. Our findings open new perspectives to study the role of HERVs in the biological mechanisms underlying Autism.
Sections du résumé
BACKGROUND
Putative pathogenic effects mediated by human endogenous retroviruses (HERVs) in neurological and psychiatric disorders in humans have been extensively described. HERVs may alter the development of the brain by means of several mechanisms, including modulation of gene expression, alteration of DNA stability, and activation of immune system. We recently demonstrated that autistic children and their mothers share high expression levels of some HERVs and cytokines in peripheral blood mononuclear cells (PBMCs) ex vivo, suggesting a close mother-child association in Autism Spectrum Disorder (ASD).
RESULTS
In the present study, PBMCs from autistic children and their parents were exposed to stimulating factors (Interleukin-2/Phytohaemagglutinin) or drugs, as Valproic acid and Efavirenz. The results show that HERVs and cytokines expression can be modulated in vitro by different stimuli in PBMCs from autistic children and their mothers, while no significant changes were found in PBMCs ASD fathers or in controls individuals. In particular, in vitro exposure to interleukin-2/Phytohaemagglutinin or valproic acid induces the expression of several HERVs and cytokines while Efavirenz inhibits them.
CONCLUSION
Herein we show that autistic children and their mothers share an intrinsic responsiveness to in vitro microenvironmental changes in expressing HERVs and pro-inflammatory cytokines. Remarkably, the antiretroviral drug Efavirenz restores the expression of specific HERV families to values similar to those of the controls, also reducing the expression of proinflammatory cytokines but keeping the regulatory ones high. Our findings open new perspectives to study the role of HERVs in the biological mechanisms underlying Autism.
Identifiants
pubmed: 36451209
doi: 10.1186/s12977-022-00603-6
pii: 10.1186/s12977-022-00603-6
pmc: PMC9709758
doi:
Substances chimiques
efavirenz
JE6H2O27P8
Cytokines
0
Interleukin-2
0
Phytohemagglutinins
0
Valproic Acid
614OI1Z5WI
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
26Informations de copyright
© 2022. The Author(s).
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