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Fig. 1 | BMC Rheumatology

Fig. 1

From: The PD-1:PD-L1 axis in Inflammatory Arthritis

Fig. 1

Mechanisms of action of PD-1. During immunological synapse formation, ligation of PD-1 with PD-L1 leads to the recruitment of SHP-2 at the ITSM site of PD-1 and subsequent dephosphorylation of PI3K, AKT and RAS dampening down TCR mediated signalling, top left panel. Due to inhibition of PI3K and RAS, PD-1 can change the metabolic profile of the T cell by limiting GLUT-1 expression and mitochondrial availability of glucose, favouring fatty acid oxidation over glycolysis, top right panel. There is a paucity of data on the role of B cell PD-1, however it has been suggested that PD-1 leads to inhibition of SYK resulting in reduced B cell proliferation and cytokine production following B cell receptor (BCR) mediated activation, bottom left panel. A recently proposed mechanism of action for macrophage PD-1 expression is binding to PDL-1 in cis and therefore limiting available PD-L1 for ligation with T cell PD-1, bottom right panel

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