ERK Inhibition Promotes Engraftment of Allografts by Reprogramming T‐Cell Metabolism
Abstract: Extracellular regulated protein kinases (ERK) signaling is a master regulator of cell behavior, life, and fate. Although ERK pathway is shown to be involved in T‐cell activation, little is known about its role in the development of allograft rejection. Here, it is reported that ERK signaling pathway is activated in allograft‐infiltrating T cells. On the basis of surface plasmon resonance technology, lycorine is identified as an ERK‐specific inhibitor. ERK inhibition by lycorine significantly prolongs allograft survival in a stringent mouse cardiac allotransplant model. As compared to untreated mice, lycorine‐treated mice show a decrease in the number and activation of allograft‐infiltrated T cells. It is further confirmed that lycorine‐treated mouse and human T cells are less responsive to stimulation in vitro, as indicated by their low proliferative rates and decreased cytokine production. Mechanistic studies reveal that T cells treated with lycorine exhibit mitochondrial dysfunction, resulting in metabolic reprogramming upon stimulation. Transcriptome analysis of lycorine‐treated T cells reveals an enrichment in a series of downregulated terms related to immune response, the mitogen‐activated protein kinase cascade, and metabolic processes. These findings offer new insights into the development of immunosuppressive agents by targeting the ERK pathway involved in T‐cell activation and allograft rejection.
- Standort
-
Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
-
Online-Ressource
- Sprache
-
Englisch
- Erschienen in
-
ERK Inhibition Promotes Engraftment of Allografts by Reprogramming T‐Cell Metabolism ; day:04 ; month:04 ; year:2023 ; extent:18
Advanced science ; (04.04.2023) (gesamt 18)
- Urheber
-
Tan, Xiaosheng
Qi, Changxing
Zhao, Xiangli
Sun, Lingjuan
Wu, Mi
Sun, Weiguang
Gu, Lianghu
Wang, Fengqing
Feng, Hao
Huang, Xia
Xie, Bin
Shi, Zhengyi
Xie, Peiling
Wu, Meng
Zhang, Yonghui
Chen, Gang
- DOI
-
10.1002/advs.202206768
- URN
-
urn:nbn:de:101:1-2023040415254552406492
- Rechteinformation
-
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
-
14.08.2025, 10:51 MESZ
Datenpartner
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Beteiligte
- Tan, Xiaosheng
- Qi, Changxing
- Zhao, Xiangli
- Sun, Lingjuan
- Wu, Mi
- Sun, Weiguang
- Gu, Lianghu
- Wang, Fengqing
- Feng, Hao
- Huang, Xia
- Xie, Bin
- Shi, Zhengyi
- Xie, Peiling
- Wu, Meng
- Zhang, Yonghui
- Chen, Gang
Ähnliche Objekte (12)
The decreased SIRT1 level may account for the lipid profile in chronic kidney disease
Competence of pharmacy mentors: a survey of the perceptions of pharmacy postgraduates and their mentors
Filling the psycho-social gap in the EQ-5D: the empirical support for four bolt-on dimensions
Spiro indane-1,3-dione pyrrolizidine compounds synthesized by 1,3-dipolar cyclo-addition reaction
TGF-β1 increases proliferation of airway smooth muscle cells by phosphorylation of map kinases
On multidimensional Schur rings of finite groups
Amplitude relations in non-linear sigma model
Infinite critical boson non-Fermi liquid on heterostructure interfaces
Synthesis, regiochemistry and molecular structure of spiro (2,2′) indane-1′,3′-dione-pyrrolizidine compounds
Study on Hermite-Hadamard-type inequalities using a new generalized fractional integral operator
Synthesis and application of polyaminoamide as new paraffin inhibitor from vegetable oil
Identification of potential DNA methylation biomarkers related to diagnosis in patients with bladder cancer through integrated bioinformatic analysis
The decreased SIRT1 level may account for the lipid profile in chronic kidney disease
Competence of pharmacy mentors: a survey of the perceptions of pharmacy postgraduates and their mentors
Filling the psycho-social gap in the EQ-5D: the empirical support for four bolt-on dimensions
Spiro indane-1,3-dione pyrrolizidine compounds synthesized by 1,3-dipolar cyclo-addition reaction
TGF-β1 increases proliferation of airway smooth muscle cells by phosphorylation of map kinases
On multidimensional Schur rings of finite groups
Amplitude relations in non-linear sigma model
Infinite critical boson non-Fermi liquid on heterostructure interfaces
Synthesis, regiochemistry and molecular structure of spiro (2,2′) indane-1′,3′-dione-pyrrolizidine compounds
Study on Hermite-Hadamard-type inequalities using a new generalized fractional integral operator
Synthesis and application of polyaminoamide as new paraffin inhibitor from vegetable oil
Identification of potential DNA methylation biomarkers related to diagnosis in patients with bladder cancer through integrated bioinformatic analysis
The decreased SIRT1 level may account for the lipid profile in chronic kidney disease
Competence of pharmacy mentors: a survey of the perceptions of pharmacy postgraduates and their mentors
Filling the psycho-social gap in the EQ-5D: the empirical support for four bolt-on dimensions
Spiro indane-1,3-dione pyrrolizidine compounds synthesized by 1,3-dipolar cyclo-addition reaction
TGF-β1 increases proliferation of airway smooth muscle cells by phosphorylation of map kinases
On multidimensional Schur rings of finite groups
Amplitude relations in non-linear sigma model
Infinite critical boson non-Fermi liquid on heterostructure interfaces
Synthesis, regiochemistry and molecular structure of spiro (2,2′) indane-1′,3′-dione-pyrrolizidine compounds
Study on Hermite-Hadamard-type inequalities using a new generalized fractional integral operator
Synthesis and application of polyaminoamide as new paraffin inhibitor from vegetable oil