Heterogeneity and mitochondrial vulnerability configurate the divergent immunoreactivity of human induced microglia-like cells

Kousuke Yonemoto; Fumihiko Fujii; Ryoji Taira; Masahiro Ohgidani; Katsuhide Eguchi; Sayaka Kawaguchi; Yuko Ichimiya; Yuri Sonoda; Pin Fee Chong; Hironori Goto; Hikaru Kanemasa; Yoshitomo Motomura; Masataka Ishimura; Yuhki Koga; Keita Tsujimura; Takao Hashiguchi; Hiroyuki Torisu; Ryutaro Kira; Takahiro A. Kato; Yasunari Sakai; Shouichi Ohga

doi:10.1016/j.clim.2023.109756

Heterogeneity and mitochondrial vulnerability configurate the divergent immunoreactivity of human induced microglia-like cells

Kousuke Yonemoto, Fumihiko Fujii, Ryoji Taira, Masahiro Ohgidani, Katsuhide Eguchi, Sayaka Kawaguchi, Yuko Ichimiya, Yuri Sonoda, Pin Fee Chong, Hironori Goto, Hikaru Kanemasa, Yoshitomo Motomura, Masataka Ishimura, Yuhki Koga, Keita Tsujimura, Takao Hashiguchi, Hiroyuki Torisu, Ryutaro Kira, Takahiro A. Kato, Yasunari SakaiShouichi Ohga

Research output: Contribution to journal › Article › peer-review

1 Citation (Scopus)

Abstract

Microglia play versatile roles in progression of and protection against neuroinflammatory diseases. Little is known, however, about the mechanisms underlying the diverse reactivity of microglia to inflammatory conditions. We investigated how human induced microglia-like (iMG) cells respond to innate immune ligands. Quantitative PCR showed that poly-I:C and lipopolysaccharide (LPS) activated the expression of IL1B and TNF. Immunoreactivity of iMG did not differ between controls (n = 11) and patients with neuroinflammatory diseases (n = 24). Flow cytometry revealed that CD14^high cells expressed interleukin (IL) -1β after LPS treatment. Immunoblotting showed that poly-I:C and LPS differentially activated inflammatory pathways but commonly induced mitochondrial instability and the expression of pyruvate kinase isoform M2 (PKM2). Furthermore, a potent stimulator of PKM2 (DASA-58) alleviated IL-1β production after LPS treatment. These data indicate that heterogeneous cell populations and mitochondrial stability underlie the divergent immunoreactivity of human iMG in environments.

Original language	English
Article number	109756
Journal	Clinical Immunology
Volume	255
DOIs	https://doi.org/10.1016/j.clim.2023.109756
Publication status	Published - Oct 2023

All Science Journal Classification (ASJC) codes

Immunology and Allergy
Immunology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.clim.2023.109756

Cite this

Yonemoto, K., Fujii, F., Taira, R., Ohgidani, M., Eguchi, K., Kawaguchi, S., Ichimiya, Y., Sonoda, Y., Chong, P. F., Goto, H., Kanemasa, H., Motomura, Y., Ishimura, M., Koga, Y., Tsujimura, K., Hashiguchi, T., Torisu, H., Kira, R., Kato, T. A., ... Ohga, S. (2023). Heterogeneity and mitochondrial vulnerability configurate the divergent immunoreactivity of human induced microglia-like cells. Clinical Immunology, 255, Article 109756. https://doi.org/10.1016/j.clim.2023.109756

Yonemoto, K, Fujii, F, Taira, R, Ohgidani, M, Eguchi, K, Kawaguchi, S, Ichimiya, Y, Sonoda, Y, Chong, PF, Goto, H, Kanemasa, H, Motomura, Y , Ishimura, M, Koga, Y, Tsujimura, K, Hashiguchi, T, Torisu, H, Kira, R, Kato, TA , Sakai, Y & Ohga, S 2023, 'Heterogeneity and mitochondrial vulnerability configurate the divergent immunoreactivity of human induced microglia-like cells', Clinical Immunology, vol. 255, 109756. https://doi.org/10.1016/j.clim.2023.109756

@article{f47a8dea11004a22a067c670618326a5,

title = "Heterogeneity and mitochondrial vulnerability configurate the divergent immunoreactivity of human induced microglia-like cells",

abstract = "Microglia play versatile roles in progression of and protection against neuroinflammatory diseases. Little is known, however, about the mechanisms underlying the diverse reactivity of microglia to inflammatory conditions. We investigated how human induced microglia-like (iMG) cells respond to innate immune ligands. Quantitative PCR showed that poly-I:C and lipopolysaccharide (LPS) activated the expression of IL1B and TNF. Immunoreactivity of iMG did not differ between controls (n = 11) and patients with neuroinflammatory diseases (n = 24). Flow cytometry revealed that CD14high cells expressed interleukin (IL) -1β after LPS treatment. Immunoblotting showed that poly-I:C and LPS differentially activated inflammatory pathways but commonly induced mitochondrial instability and the expression of pyruvate kinase isoform M2 (PKM2). Furthermore, a potent stimulator of PKM2 (DASA-58) alleviated IL-1β production after LPS treatment. These data indicate that heterogeneous cell populations and mitochondrial stability underlie the divergent immunoreactivity of human iMG in environments.",

author = "Kousuke Yonemoto and Fumihiko Fujii and Ryoji Taira and Masahiro Ohgidani and Katsuhide Eguchi and Sayaka Kawaguchi and Yuko Ichimiya and Yuri Sonoda and Chong, {Pin Fee} and Hironori Goto and Hikaru Kanemasa and Yoshitomo Motomura and Masataka Ishimura and Yuhki Koga and Keita Tsujimura and Takao Hashiguchi and Hiroyuki Torisu and Ryutaro Kira and Kato, {Takahiro A.} and Yasunari Sakai and Shouichi Ohga",

note = "Publisher Copyright: {\textcopyright} 2023 Elsevier Inc.",

year = "2023",

month = oct,

doi = "10.1016/j.clim.2023.109756",

language = "English",

volume = "255",

journal = "Clinical Immunology",

issn = "1521-6616",

publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - Heterogeneity and mitochondrial vulnerability configurate the divergent immunoreactivity of human induced microglia-like cells

AU - Yonemoto, Kousuke

AU - Fujii, Fumihiko

AU - Taira, Ryoji

AU - Ohgidani, Masahiro

AU - Eguchi, Katsuhide

AU - Kawaguchi, Sayaka

AU - Ichimiya, Yuko

AU - Sonoda, Yuri

AU - Chong, Pin Fee

AU - Goto, Hironori

AU - Kanemasa, Hikaru

AU - Motomura, Yoshitomo

AU - Ishimura, Masataka

AU - Koga, Yuhki

AU - Tsujimura, Keita

AU - Hashiguchi, Takao

AU - Torisu, Hiroyuki

AU - Kira, Ryutaro

AU - Kato, Takahiro A.

AU - Sakai, Yasunari

AU - Ohga, Shouichi

PY - 2023/10

Y1 - 2023/10

N2 - Microglia play versatile roles in progression of and protection against neuroinflammatory diseases. Little is known, however, about the mechanisms underlying the diverse reactivity of microglia to inflammatory conditions. We investigated how human induced microglia-like (iMG) cells respond to innate immune ligands. Quantitative PCR showed that poly-I:C and lipopolysaccharide (LPS) activated the expression of IL1B and TNF. Immunoreactivity of iMG did not differ between controls (n = 11) and patients with neuroinflammatory diseases (n = 24). Flow cytometry revealed that CD14high cells expressed interleukin (IL) -1β after LPS treatment. Immunoblotting showed that poly-I:C and LPS differentially activated inflammatory pathways but commonly induced mitochondrial instability and the expression of pyruvate kinase isoform M2 (PKM2). Furthermore, a potent stimulator of PKM2 (DASA-58) alleviated IL-1β production after LPS treatment. These data indicate that heterogeneous cell populations and mitochondrial stability underlie the divergent immunoreactivity of human iMG in environments.

AB - Microglia play versatile roles in progression of and protection against neuroinflammatory diseases. Little is known, however, about the mechanisms underlying the diverse reactivity of microglia to inflammatory conditions. We investigated how human induced microglia-like (iMG) cells respond to innate immune ligands. Quantitative PCR showed that poly-I:C and lipopolysaccharide (LPS) activated the expression of IL1B and TNF. Immunoreactivity of iMG did not differ between controls (n = 11) and patients with neuroinflammatory diseases (n = 24). Flow cytometry revealed that CD14high cells expressed interleukin (IL) -1β after LPS treatment. Immunoblotting showed that poly-I:C and LPS differentially activated inflammatory pathways but commonly induced mitochondrial instability and the expression of pyruvate kinase isoform M2 (PKM2). Furthermore, a potent stimulator of PKM2 (DASA-58) alleviated IL-1β production after LPS treatment. These data indicate that heterogeneous cell populations and mitochondrial stability underlie the divergent immunoreactivity of human iMG in environments.

UR - http://www.scopus.com/inward/record.url?scp=85170421288&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85170421288&partnerID=8YFLogxK

U2 - 10.1016/j.clim.2023.109756

DO - 10.1016/j.clim.2023.109756

M3 - Article

C2 - 37678717

AN - SCOPUS:85170421288

SN - 1521-6616

VL - 255

JO - Clinical Immunology

JF - Clinical Immunology

M1 - 109756

ER -

Heterogeneity and mitochondrial vulnerability configurate the divergent immunoreactivity of human induced microglia-like cells

Abstract

All Science Journal Classification (ASJC) codes

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this