Publication: Activation of sympathetic signaling in macrophages blocks systemic inflammation and protects against renal ischemia-reperfusion injury
Issued Date
2021-07-01
Resource Type
ISSN
15333450
10466673
10466673
Other identifier(s)
2-s2.0-85114055765
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of the American Society of Nephrology. Vol.32, No.7 (2021), 1599-1615
Suggested Citation
Sho Hasegawa, Tsuyoshi Inoue, Yasuna Nakamura, Daichi Fukaya, Rie Uni, Chia Hsien Wu, Rie Fujii, Wachirasek Peerapanyasut, Akashi Taguchi, Takahide Kohro, Shintaro Yamada, Mikako Katagiri, Toshiyuki Ko, Seitaro Nomura, Atsuko Nakanishi Ozeki, Etsuo A. Susaki, Hiroki R. Ueda, Nobuyoshi Akimitsu, Youichiro Wada, Issei Komuro, Masaomi Nangaku, Reiko Inagi Activation of sympathetic signaling in macrophages blocks systemic inflammation and protects against renal ischemia-reperfusion injury. Journal of the American Society of Nephrology. Vol.32, No.7 (2021), 1599-1615. doi:10.1681/ASN.2020121723 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/78051
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Activation of sympathetic signaling in macrophages blocks systemic inflammation and protects against renal ischemia-reperfusion injury
Author(s)
Sho Hasegawa
Tsuyoshi Inoue
Yasuna Nakamura
Daichi Fukaya
Rie Uni
Chia Hsien Wu
Rie Fujii
Wachirasek Peerapanyasut
Akashi Taguchi
Takahide Kohro
Shintaro Yamada
Mikako Katagiri
Toshiyuki Ko
Seitaro Nomura
Atsuko Nakanishi Ozeki
Etsuo A. Susaki
Hiroki R. Ueda
Nobuyoshi Akimitsu
Youichiro Wada
Issei Komuro
Masaomi Nangaku
Reiko Inagi
Tsuyoshi Inoue
Yasuna Nakamura
Daichi Fukaya
Rie Uni
Chia Hsien Wu
Rie Fujii
Wachirasek Peerapanyasut
Akashi Taguchi
Takahide Kohro
Shintaro Yamada
Mikako Katagiri
Toshiyuki Ko
Seitaro Nomura
Atsuko Nakanishi Ozeki
Etsuo A. Susaki
Hiroki R. Ueda
Nobuyoshi Akimitsu
Youichiro Wada
Issei Komuro
Masaomi Nangaku
Reiko Inagi
Abstract
Background The sympathetic nervous system regulates immune cell dynamics. However, the detailed role of sympathetic signaling in inflammatory diseases is still unclear because it varies according to the disease situation and responsible cell types. This study focused on identifying the functions of sympathetic signaling in macrophages in LPS-induced sepsis and renal ischemia-reperfusion injury (IRI). Methods We performed RNA sequencing of mouse macrophage cell lines to identify the critical gene that mediates the anti-inflammatory effect of b2-adrenergic receptor (Adrb2) signaling. We also examined the effects of salbutamol (a selective Adrb2 agonist) in LPS-induced systemic inflammation and renal IRI. Macrophage-specific Adrb2 conditional knockout (cKO) mice and the adoptive transfer of salbutamol-treated macrophages were used to assess the involvement of macrophage Adrb2 signaling. Results In vitro, activation of Adrb2 signaling in macrophages induced the expression of T cell Ig and mucin domain 3 (Tim3), which contributes to anti-inflammatory phenotypic alterations. In vivo, salbutamol administration blocked LPS-induced systemic inflammation and protected against renal IRI; this protection was mitigated in macrophage-specific Adrb2 cKO mice. The adoptive transfer of salbutamol-treated macrophages also protected against renal IRI. Single-cell RNA sequencing revealed that this protection was associated with the accumulation of Tim3-expressing macrophages in the renal tissue. Conclusions The activation of Adrb2 signaling in macrophages induces anti-inflammatory phenotypic alterations partially via the induction of Tim3 expression, which blocks LPS-induced systemic inflammation and protects against renal IRI.