CMRF35-like molecule 1 (CLM-1)

CMRF35-like molecule 1 (CLM-1), also known as CD300f or leukocyte mono-immunoglobulin-like receptor 3 (LMIR3), is a type I transmembrane inhibitory and activating immune receptor primarily expressed on myeloid-lineage cells, including mast cells, microglia, and some monocytes[2][3]. CLM-1 is part of the CD300 family and features two immunoreceptor tyrosine-based inhibitory motifs (ITIMs) and one immunoreceptor tyrosine-based switch motif (ITSM) in its long cytoplasmic domain, allowing it to recruit phosphatases (such as SHP-1 and SHP-2) to suppress immune cell activation. Additionally, CLM-1 can activate signaling via interaction with the p85α subunit of PI3K and the adaptor Grb2, facilitating phagocytosis of apoptotic cells. Exogenous ligands like ceramide and endogenous interactions enable CLM-1 to negatively regulate FcεRI- and MRGPRX2-mediated mast cell degranulation and cytokine production, modulating allergic and inflammatory responses[3]. CLM-1 also exists as a soluble isoform and regulates microglial activation, and its absence exacerbates allergic, inflammatory, and immune-mediated processes in murine models, suggesting its importance as a modulatory checkpoint in immunity and as a potential therapeutic target[2][3].

Other names

Leukocyte mono-immunoglobulin-like receptor 3 (LMIR3)CD300fCD300 antigen-like family member FIREM-1

Inhibition of immune cell activation via ITIM (Immunoreceptor Tyrosine-based Inhibitory Motif)-mediated phosphatase recruitment (e.g. SHP-1, SHP-2); Negative modulation of FcεRI and MRGPRX2 signaling pathways; Promotion of apoptotic cell engulfment via PI3K pathway