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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Front+Immunol
2017 ; 8
(ä): 330
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gab.com Text
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Twit Text #
English Wikipedia
Immunometabolic Regulations Mediated by Coinhibitory Receptors and Their Impact
on T Cell Immune Responses
#MMPMID28443090
Patsoukis N
; Weaver JD
; Strauss L
; Herbel C
; Seth P
; Boussiotis VA
Front Immunol
2017[]; 8
(ä): 330
PMID28443090
show ga
Host immunity provides wide spectrum protection that serves to eradicate
pathogens and cancer cells, while maintaining self-tolerance and immunological
homeostasis. Ligation of the T cell receptor (TCR) by antigen activates signaling
pathways that coordinately induce aerobic glycolysis, mitochondrial activity,
anabolic metabolism, and T effector cell differentiation. Activation of PI3K,
Akt, and mTOR triggers the switch to anabolic metabolism by inducing
transcription factors such as Myc and HIF1, and the glucose transporter Glut1,
which is pivotal for the increase of glucose uptake after T cell activation.
Activation of MAPK signaling is required for glucose and glutamine utilization,
whereas activation of AMPK is critical for energy balance and metabolic fitness
of T effector and memory cells. Coinhibitory receptors target TCR-proximal
signaling and generation of second messengers. Imbalanced activation of such
signaling pathways leads to diminished rates of aerobic glycolysis and impaired
mitochondrial function resulting in defective anabolic metabolism and altered T
cell differentiation. The coinhibitory receptors mediate distinct and synergistic
effects on the activation of signaling pathways thereby modifying metabolic
programs of activated T cells and resulting in altered immune functions.
Understanding and therapeutic targeting of metabolic programs impacted by
coinhibitory receptors might have significant clinical implications for the
treatment of chronic infections, cancer, and autoimmune diseases.