Triggering receptor expressed on myeloid cells 2 and DNAX-activation protein 12 signaling complex (TREM2/DAP12)

Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane receptor primarily expressed on microglia in the central nervous system and macrophages in peripheral tissues. TREM2 lacks an intrinsic signaling domain and must associate with the adapter protein DNAX-activation protein 12 (DAP12), also known as TYROBP, to initiate downstream signaling via its Immunoreceptor Tyrosine-based Activation Motif (ITAM). This signaling complex is vital for microglial functions, including the sensing of lipids, apoptotic neurons, and amyloid-beta plaques, as well as promoting cell survival and phagocytic clearance. In neurodegenerative disorders such as Alzheimer's disease, loss-of-function mutations in TREM2 are linked to increased disease risk due to impaired microglial response to pathology. Conversely, in oncology, TREM2-expressing tumor-associated macrophages can promote an immunosuppressive environment, making the pathway a target for both agonistic antibodies in neurology and inhibitory strategies in cancer immunotherapy.

Other names

TREM2/TYROBP complexTriggering receptor expressed on myeloid cells 2TYRO protein tyrosine kinase-binding proteinDAP12CD354TREM-2

Agonism (activating the receptor to enhance microglial phagocytosis and survival in neurodegeneration) or Antagonism (inhibiting the receptor to reduce immunosuppression in the tumor microenvironment)