Moreover, this family of receptors has great potential as targets for diagnosis and therapeutic purposes in infectious diseases, allergies, cancer, and other pathological situations. For instance, one member of the family, CD300a, has been studied as a possible biomarker. Here, a review is usually provided around the cellular distribution of the human and mouse families of receptors, the stimuli that regulate their expression, their ability to tune leukocyte function and immune responses, their signaling pathways, ligand recognition, and their clinical relevance. Introduction In order to provide an adequate response that allows the elimination of insults while preserving self, the immune system is Smad7 usually tightly regulated by a balance between activating and inhibitory signals. Multiple mechanisms exist to accomplish this task, including the expression of activating and inhibitory receptors by immune cells.1-5 In general, the inhibitory receptors carry immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in their cytoplasmic tail,2,4 whereas their activating counterparts have a charged residue in GR 103691 their transmembrane segments that facilitates the interaction with adaptor proteins carrying immunoreceptor tyrosine-based activating motifs or phosphatidylinositol 3-kinase (PI3K) binding motif (YxxM).2,6 The human CD300 multigene family has 7 members located on chromosome 17.7-9 They were named alphabetically according to the order of their location in the chromosome. The mouse counterparts, which were reported as dendritic cell (DC)Cderived Ig-like receptor (DIgR),10 CMRF-35Clike molecules (CLM),11 leukocyte monoCIg-like receptor (LMIR),12 GR 103691 and myeloid-associated Ig-like receptor (MAIR),13 are encoded by 9 genes located on mouse chromosome 11, the synthenic region of human chromosome 17.9 The human-mouse CD300 orthologs have been identified by phylogenetic analysis and by their gene organization within the complex.9 However, except for the 2 2 inhibitory receptors (ie, CD300a and CD300f), all the others are not perfect functional orthologs. For the purpose of clarity, and based on the published literature, this review will use the CD nomenclature for the human molecules and for the 2 2 murine ITIM-containing receptors. For the rest of the mouse CD300 molecules, the nomenclature is still very confusing, and in this review, sometimes a combination of names will be used when referring to the same receptor. Table 1 and Table 2 summarize the nomenclature these receptors have received since their discoveries. In Physique 1, the genomic business of the human and mouse CD300 complexes is usually represented according to the latest drafts provided by the National Center for Biotechnology Information (NCBI; http://www.ncbi.nlm.nih.gov/gene) and the Mouse Genomic Informatics (MGI; http://www.informatics.jax.org). For the murine genes, the CD nomenclature has not been used for all the genes in Physique 1, but it is usually shown in Table 2. Table 1 Human CD300 family members Since the initial submission GR 103691 of this review, Takahashi et al. have shown that human CD300c is usually expressed around the cell surface of monocytes and mast cells, is able to deliver an activating signal after cross-linking with specific mAbs and recognizes the aminophospholipid PE (Takahashi et al. Human CD300C delivers an Fc receptor-gamma-dependent activating signal in mast cells and monocytes and differs from CD300A on ligand recognition. em J Biol Chem /em , in press, 2013). Authorship Contribution: F.B. wrote the manuscript. Conflict-of-interest disclosure: The author declares no GR 103691 competing financial interest. Correspondence: Francisco Borrego, Laboratory of Molecular and Developmental Immunology, Division of Monoclonal Antibodies, Office of Biotechnology Products, Center for Drug Evaluation and Research, Food and Drug Administration, Building 29B, Room 3NN18, GR 103691 29 Lincoln Dr, HFD-123, Bethesda, MD 20892; e-mail: vog.shh.adf@ogerrob.ocsicnarf; moc.liamg@ocsabarogerrobocap.