Spleen tyrosine kinase-Phosphoinositide 3-kinase-Nuclear factor kappa B signaling pathway (Syk-PI3K-NF-κB pathway)

The Spleen tyrosine kinase-Phosphoinositide 3-kinase-Nuclear factor kappa B (Syk-PI3K-NF-κB) signaling pathway is a critical intracellular cascade that mediates the activation and maturation of dendritic cells (DCs) in response to various stimuli, particularly through C-type lectin receptors (CLRs) like Dectin-1 and Dectin-2 [PMID: 17448156, 21525984]. Upon ligand binding, Syk is recruited to phosphorylated immunoreceptor tyrosine-based activation motifs (ITAMs), triggering downstream activation of PI3K [PMID: 19234452]. This cascade ultimately leads to the activation and nuclear translocation of NF-κB, which drives the expression of pro-inflammatory cytokines and costimulatory molecules necessary for T-cell priming [PMID: 23601688]. This pathway plays a pivotal role in orchestrating innate and adaptive immune responses against fungal and bacterial pathogens [PMID: 28978534]. Pharmacological targeting of individual components, such as Syk or PI3K, is a therapeutic strategy used to modulate immune responses in inflammatory, autoimmune, and hematological disorders [PMID: 30333114].

Other names

Syk-PI3K-NF-kappaB pathwayDendritic cell activation pathwayCLR-Syk signaling cascadeSyk-dependent signaling in dendritic cells

Inhibition of Spleen tyrosine kinase (Syk) activity, inhibition of Phosphoinositide 3-kinase (PI3K) isoforms, or inhibition of the NF-kappaB activation pathway to modulate immune cell function.