[article]
| Titre : |
Granulocyte macrophage colony-stimulating factor-induced macrophages of individuals with autism spectrum disorder adversely affect neuronal dendrites through the secretion of pro-inflammatory cytokines |
| Type de document : |
Texte imprimé et/ou numérique |
| Auteurs : |
Ryohei TAKADA, Auteur ; Michihiro TORITSUKA, Auteur ; Takahira YAMAUCHI, Auteur ; Rio ISHIDA, Auteur ; Yoshinori KAYASHIMA, Auteur ; Yuki NISHI, Auteur ; Mitsuru ISHIKAWA, Auteur ; Kazuhiko YAMAMURO, Auteur ; Minobu IKEHARA, Auteur ; Takashi KOMORI, Auteur ; Yuki NORIYAMA, Auteur ; Kohei KAMIKAWA, Auteur ; Yasuhiko SAITO, Auteur ; Hideyuki OKANO, Auteur ; Manabu MAKINODAN, Auteur |
| Article en page(s) : |
10p. |
| Langues : |
Anglais (eng) |
| Mots-clés : |
Female Male Humans Cytokines Granulocyte-Macrophage Colony-Stimulating Factor/metabolism/pharmacology Macrophage Colony-Stimulating Factor/metabolism/pharmacology Tumor Necrosis Factor-alpha/metabolism/pharmacology Leukocytes, Mononuclear/metabolism Interleukin-1alpha/metabolism/pharmacology Autism Spectrum Disorder/metabolism Cells, Cultured Sexism Macrophages/metabolism Granulocytes/metabolism Dendrites/metabolism Autism spectrum disorder Dendrite Human iPS cell Interleukin-1? Macrophage Tumor necrosis factor-? |
| Index. décimale : |
PER Périodiques |
| Résumé : |
BACKGROUND: A growing body of evidence suggests that immune dysfunction and inflammation in the peripheral tissues as well as the central nervous system are associated with the neurodevelopmental deficits observed in autism spectrum disorder (ASD). Elevated expression of pro-inflammatory cytokines in the plasma, serum, and peripheral blood mononuclear cells of ASD has been reported. These cytokine expression levels are associated with the severity of behavioral impairments and symptoms in ASD. In a prior study, our group reported that tumor necrosis factor-? (TNF-?) expression in granulocyte-macrophage colony-stimulating factor-induced macrophages (GM-CSF M?) and the TNF-? expression ratio in GM-CSF M?/M-CSF M? (macrophage colony-stimulating factor-induced macrophages) was markedly higher in individuals with ASD than in typically developed (TD) individuals. However, the mechanisms of how the macrophages and the highly expressed cytokines affect neurons remain to be addressed. METHODS: To elucidate the effect of macrophages on human neurons, we used a co-culture system of control human-induced pluripotent stem cell-derived neurons and differentiated macrophages obtained from the peripheral blood mononuclear cells of five TD individuals and five individuals with ASD. All participants were male and ethnically Japanese. RESULTS: Our results of co-culture experiments showed that GM-CSF M? affect the dendritic outgrowth of neurons through the secretion of pro-inflammatory cytokines, interleukin-1? and TNF-?. Macrophages derived from individuals with ASD exerted more severe effects than those derived from TD individuals. LIMITATIONS: The main limitations of our study were the small sample size with a gender bias toward males, the use of artificially polarized macrophages, and the inability to directly observe the interaction between neurons and macrophages from the same individuals. CONCLUSIONS: Our co-culture system revealed the non-cell autonomous adverse effects of GM-CSF M? in individuals with ASD on neurons, mediated by interleukin-1? and TNF-?. These results may support the immune dysfunction hypothesis of ASD, providing new insights into its pathology. |
| En ligne : |
https://dx.doi.org/10.1186/s13229-024-00589-2 |
| Permalink : |
https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 |
in Molecular Autism > 15 (2024) . - 10p.
[article] Granulocyte macrophage colony-stimulating factor-induced macrophages of individuals with autism spectrum disorder adversely affect neuronal dendrites through the secretion of pro-inflammatory cytokines [Texte imprimé et/ou numérique] / Ryohei TAKADA, Auteur ; Michihiro TORITSUKA, Auteur ; Takahira YAMAUCHI, Auteur ; Rio ISHIDA, Auteur ; Yoshinori KAYASHIMA, Auteur ; Yuki NISHI, Auteur ; Mitsuru ISHIKAWA, Auteur ; Kazuhiko YAMAMURO, Auteur ; Minobu IKEHARA, Auteur ; Takashi KOMORI, Auteur ; Yuki NORIYAMA, Auteur ; Kohei KAMIKAWA, Auteur ; Yasuhiko SAITO, Auteur ; Hideyuki OKANO, Auteur ; Manabu MAKINODAN, Auteur . - 10p. Langues : Anglais ( eng) in Molecular Autism > 15 (2024) . - 10p.
| Mots-clés : |
Female Male Humans Cytokines Granulocyte-Macrophage Colony-Stimulating Factor/metabolism/pharmacology Macrophage Colony-Stimulating Factor/metabolism/pharmacology Tumor Necrosis Factor-alpha/metabolism/pharmacology Leukocytes, Mononuclear/metabolism Interleukin-1alpha/metabolism/pharmacology Autism Spectrum Disorder/metabolism Cells, Cultured Sexism Macrophages/metabolism Granulocytes/metabolism Dendrites/metabolism Autism spectrum disorder Dendrite Human iPS cell Interleukin-1? Macrophage Tumor necrosis factor-? |
| Index. décimale : |
PER Périodiques |
| Résumé : |
BACKGROUND: A growing body of evidence suggests that immune dysfunction and inflammation in the peripheral tissues as well as the central nervous system are associated with the neurodevelopmental deficits observed in autism spectrum disorder (ASD). Elevated expression of pro-inflammatory cytokines in the plasma, serum, and peripheral blood mononuclear cells of ASD has been reported. These cytokine expression levels are associated with the severity of behavioral impairments and symptoms in ASD. In a prior study, our group reported that tumor necrosis factor-? (TNF-?) expression in granulocyte-macrophage colony-stimulating factor-induced macrophages (GM-CSF M?) and the TNF-? expression ratio in GM-CSF M?/M-CSF M? (macrophage colony-stimulating factor-induced macrophages) was markedly higher in individuals with ASD than in typically developed (TD) individuals. However, the mechanisms of how the macrophages and the highly expressed cytokines affect neurons remain to be addressed. METHODS: To elucidate the effect of macrophages on human neurons, we used a co-culture system of control human-induced pluripotent stem cell-derived neurons and differentiated macrophages obtained from the peripheral blood mononuclear cells of five TD individuals and five individuals with ASD. All participants were male and ethnically Japanese. RESULTS: Our results of co-culture experiments showed that GM-CSF M? affect the dendritic outgrowth of neurons through the secretion of pro-inflammatory cytokines, interleukin-1? and TNF-?. Macrophages derived from individuals with ASD exerted more severe effects than those derived from TD individuals. LIMITATIONS: The main limitations of our study were the small sample size with a gender bias toward males, the use of artificially polarized macrophages, and the inability to directly observe the interaction between neurons and macrophages from the same individuals. CONCLUSIONS: Our co-culture system revealed the non-cell autonomous adverse effects of GM-CSF M? in individuals with ASD on neurons, mediated by interleukin-1? and TNF-?. These results may support the immune dysfunction hypothesis of ASD, providing new insights into its pathology. |
| En ligne : |
https://dx.doi.org/10.1186/s13229-024-00589-2 |
| Permalink : |
https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 |
|
Granulocyte macrophage colony-stimulating factor-induced macrophages of individuals with autism spectrum disorder adversely affect neuronal dendrites through the secretion of pro-inflammatory cytokines in Molecular Autism, 15 (2024)
