Granulocyte macrophage colony-stimulating factor-induced macrophages of individuals with autism spectrum disorder adversely affect neuronal dendrites through the secretion of pro-inflammatory cytokines / Ryohei TAKADA in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 10p. 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 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 [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] / 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

Tumor necrosis factor-α expression aberration of M1/M2 macrophages in adult high-functioning autism spectrum disorder / Takahira YAMAUCHI in Autism Research, 14-11 (November 2021)  

Public ISBD [article]  inAutism Research > 14-11 (November 2021) . - p.2330-2341 Titre : Tumor necrosis factor-α expression aberration of M1/M2 macrophages in adult high-functioning autism spectrum disorder Type de document : texte imprimé Auteurs : Takahira YAMAUCHI, Auteur ; Manabu MAKINODAN, Auteur ; Michihiro TORITSUKA, Auteur ; Kazuki OKUMURA, Auteur ; Yoshinori KAYASHIMA, Auteur ; Rie ISHIDA, Auteur ; Naoko KISHIMOTO, Auteur ; Masato TAKAHASHI, Auteur ; Takashi KOMORI, Auteur ; Yasunari YAMAGUCHI, Auteur ; Ryohei TAKADA, Auteur ; Kazuhiko YAMAMURO, Auteur ; Sohei KIMOTO, Auteur ; Yuka YASUDA, Auteur ; Ryota HASHIMOTO, Auteur ; Naoko KISHIMOTO, Auteur Article en page(s) : p.2330-2341 Langues : Anglais (eng) Mots-clés : Adult  Autism Spectrum Disorder  Cytokines  Humans  Macrophages  Monocytes  Tumor Necrosis Factor-alpha  Tnf-?  diagnosis  inflammation  macrophage  monocyte Index. décimale : PER Périodiques Résumé : The etiology of autism spectrum disorder (ASD) is complex, and its pathobiology is characterized by enhanced inflammatory activities; however, the precise pathobiology and underlying causes of ASD remain unclear. This study was performed to identify inflammatory indicators useful for diagnosing ASD. The mRNA expression of cytokines, including tumor necrosis factor-α (TNF-α), was measured in cultured M1 and M2 macrophages from patients with ASD (n = 29) and typically developed (TD) individuals (n = 30). Additionally, TNF-α expression in the monocytes of patients with ASD (n = 7), showing aberrations in TNF-α expression in M1/M2 macrophages and TD individuals (n = 6), was measured. TNF-α expression in M1 macrophages and the TNF-α expression ratio in M1/M2 macrophages were markedly higher in patients with ASD than in TD individuals; however, this increase was not observed in M2 macrophages (M1: sensitivity = 34.5%, specificity = 96.7%, area under the curve = 0.74, positive likelihood ratio = 10.34; ratio of M1/M2: sensitivity = 55.2%, specificity = 96.7%, area under the curve = 0.79, positive likelihood ratio = 16.55). Additionally, TNF-α expression in monocytes did not significantly differ between patients with ASD and TD individuals. In conclusion, further studies on TNF-α expression in cultured macrophages may improve the understanding of ASD pathobiology. LAY SUMMARY: TNF-α expression in differentiated M1 macrophages and TNF-α expression ratio in differentiated M1/M2 macrophages were markedly higher in patients with ASD than in TD individuals, while no difference in TNF-α expression was found in pre-differentiation cells such as monocytes. These measurements allow elucidation of the novel pathobiology of ASD and can contribute to biomarker implementation for the diagnosis of adult high-functioning ASD. En ligne : http://dx.doi.org/10.1002/aur.2585 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=450 [article] Tumor necrosis factor-α expression aberration of M1/M2 macrophages in adult high-functioning autism spectrum disorder [texte imprimé] / Takahira YAMAUCHI, Auteur ; Manabu MAKINODAN, Auteur ; Michihiro TORITSUKA, Auteur ; Kazuki OKUMURA, Auteur ; Yoshinori KAYASHIMA, Auteur ; Rie ISHIDA, Auteur ; Naoko KISHIMOTO, Auteur ; Masato TAKAHASHI, Auteur ; Takashi KOMORI, Auteur ; Yasunari YAMAGUCHI, Auteur ; Ryohei TAKADA, Auteur ; Kazuhiko YAMAMURO, Auteur ; Sohei KIMOTO, Auteur ; Yuka YASUDA, Auteur ; Ryota HASHIMOTO, Auteur ; Naoko KISHIMOTO, Auteur . - p.2330-2341. Langues : Anglais (eng) in Autism Research > 14-11 (November 2021) . - p.2330-2341 Mots-clés : Adult  Autism Spectrum Disorder  Cytokines  Humans  Macrophages  Monocytes  Tumor Necrosis Factor-alpha  Tnf-?  diagnosis  inflammation  macrophage  monocyte Index. décimale : PER Périodiques Résumé : The etiology of autism spectrum disorder (ASD) is complex, and its pathobiology is characterized by enhanced inflammatory activities; however, the precise pathobiology and underlying causes of ASD remain unclear. This study was performed to identify inflammatory indicators useful for diagnosing ASD. The mRNA expression of cytokines, including tumor necrosis factor-α (TNF-α), was measured in cultured M1 and M2 macrophages from patients with ASD (n = 29) and typically developed (TD) individuals (n = 30). Additionally, TNF-α expression in the monocytes of patients with ASD (n = 7), showing aberrations in TNF-α expression in M1/M2 macrophages and TD individuals (n = 6), was measured. TNF-α expression in M1 macrophages and the TNF-α expression ratio in M1/M2 macrophages were markedly higher in patients with ASD than in TD individuals; however, this increase was not observed in M2 macrophages (M1: sensitivity = 34.5%, specificity = 96.7%, area under the curve = 0.74, positive likelihood ratio = 10.34; ratio of M1/M2: sensitivity = 55.2%, specificity = 96.7%, area under the curve = 0.79, positive likelihood ratio = 16.55). Additionally, TNF-α expression in monocytes did not significantly differ between patients with ASD and TD individuals. In conclusion, further studies on TNF-α expression in cultured macrophages may improve the understanding of ASD pathobiology. LAY SUMMARY: TNF-α expression in differentiated M1 macrophages and TNF-α expression ratio in differentiated M1/M2 macrophages were markedly higher in patients with ASD than in TD individuals, while no difference in TNF-α expression was found in pre-differentiation cells such as monocytes. These measurements allow elucidation of the novel pathobiology of ASD and can contribute to biomarker implementation for the diagnosis of adult high-functioning ASD. En ligne : http://dx.doi.org/10.1002/aur.2585 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=450

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