Immunoreceptor tyrosine-based activation motif-containing receptor (ITAM receptor)

Monocyte/macrophage ITAM receptors are a diverse group of cell surface proteins characterized by their use of Immunoreceptor Tyrosine-based Activation Motifs (ITAMs) for intracellular signaling. These receptors, which include the Fc gamma receptor (FcγR) family, Triggering Receptor Expressed on Myeloid cells (TREM) family, and certain C-type lectins, play a critical role in the innate immune response by regulating phagocytosis, cytokine release, and cell survival (PMID: 25061877, PMID: 32655581). In disease states, dysregulated ITAM signaling contributes to chronic inflammation, autoimmune disorders like rheumatoid arthritis, and the immunosuppressive environment of tumors (PMID: 25061877, PMID: 39263144). Conversely, certain ITAM receptors like TREM2 are vital for clearing debris in neurodegenerative conditions such as Alzheimer's disease (PMID: 39263144). Therapeutic strategies involve either activating these receptors to enhance immune clearance or inhibiting them to dampen pathological inflammation, with several monoclonal antibodies and small molecule inhibitors of downstream kinases like Syk currently in clinical development (PMID: 39263144, PMID: 33868317). The modulation of these receptors offers a pathway to fine-tune the myeloid response in various pathological contexts (PMID: 24711621, PMID: 23105139).

Other names

ITAM-bearing receptorMyeloid ITAM receptorActivating myeloid receptorITAM-coupled receptor

Modulation of ITAM-mediated signaling through recruitment of Syk kinase for activation or SHP-1 phosphatase for inhibitory signaling (ITAMi).