SIGLEC8
SIGLEC8 is a member of the SIGLEC (sialic acid-binding immunoglobulin-like lectins) family of proteins, which are found on the surface of immune cells. SIGLEC8 is specifically expressed on eosinophils, mast cells, and basophils, and plays a crucial role in the regulation of these cells' functions.
Structure
SIGLEC8 is a type I transmembrane protein that consists of an extracellular region, a transmembrane region, and a cytoplasmic tail. The extracellular region contains a V-set immunoglobulin domain that binds to sialic acid-containing ligands, and two C2-set immunoglobulin domains. The cytoplasmic tail contains an immunoreceptor tyrosine-based inhibitory motif (ITIM) and an immunoreceptor tyrosine-based switch motif (ITSM), which are involved in intracellular signaling.
Function
SIGLEC8 is involved in the regulation of immune responses. When it binds to its ligands, it can inhibit the activation and proliferation of eosinophils, mast cells, and basophils. This can help to prevent excessive immune responses and inflammation. In addition, SIGLEC8 can induce apoptosis (programmed cell death) in eosinophils and mast cells, which can help to resolve inflammation.
Clinical significance
Because of its role in regulating immune responses, SIGLEC8 is a potential target for the treatment of diseases that involve eosinophils, mast cells, and basophils. These include asthma, allergic rhinitis, atopic dermatitis, and eosinophilic esophagitis. Several drugs that target SIGLEC8 are currently being developed and tested in clinical trials.
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Contributors: Prab R. Tumpati, MD