Triggering receptor expressed on myeloid cells (TREM) serves to modulate the immune response stimulated by pathogen recognition receptors like TLR and cytokine receptors like IL-1R. TREM is expressed on a number of innate immune cells, including macrophages, dendritic cells, monocytes, and neutrophils. Upon binding of ligand to TREM, the receptor initiates signaling through DAP12’s tyrosine-based activation motif (ITAM). Phosphorylated ITAMs allow for binding of Syk kinase which can drive activation of the PI3K and Akt pathways, and thereby promote survival of inflammatory cells by inhibiting apoptosis. Inflammatory signals from stimulation of IL-1R and TLRs can induce NF-κB transcriptional activity, and TREM signaling can regulate this response through ERK activation.
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