CD300 molecule-like family member f (CD300f) (CD300f)

CD300 molecule-like family member f (CD300f), also known as CLM-1 or LMIR3, is a type I transmembrane protein and a member of the CD300 family of immunoregulatory receptors (UniProt KB: Q8TDQ1). It is highly expressed on myeloid cells, particularly mast cells, where it serves as a potent inhibitory receptor. Upon binding to its ligands, such as ceramide or sphingomyelin exposed on apoptotic cells, CD300f utilizes its cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs) to recruit phosphatases like SHP-1 and SHP-2 (Izawa et al., 2007, J. Exp. Med.). These phosphatases dampen activating signals from receptors like FcεRI, thereby inhibiting mast cell degranulation and the release of pro-inflammatory mediators. This inhibitory action makes CD300f a significant regulator of allergic responses, asthma, and anaphylaxis (Can et al., 2008, J. Immunol.). In addition to its role in mast cell stabilization, CD300f is involved in the clearance of apoptotic cells (efferocytosis), a process essential for maintaining tissue homeostasis and preventing autoimmunity (Munitz et al., 2006, Blood). While no therapeutic agents targeting CD300f are currently FDA-approved, it is being actively researched as a target for agonist-based therapies to treat mast cell-driven pathologies. Potential safety concerns include systemic immunosuppression and the impairment of apoptotic cell clearance, which could lead to the accumulation of secondary necrotic debris.

Other names

CLM-1CMRF35-like molecule 1LMIR3IGSF13CD300LFDIREM

Agonism of the CD300f receptor triggers the phosphorylation of its cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs), leading to the recruitment of SHP-1 and SHP-2 phosphatases. these phosphatases dephosphorylate key signaling molecules in the FcεRI pathway, effectively inhibiting mast cell degranulation and the release of pro-inflammatory mediators.