CD300a, an inhibitory receptor of the CD300 molecule family, is a type I transmembrane glycoprotein expressed on the cell membrane of human and other mammals [1]. It is broadly expressed on myeloid and lymphoid cells and plays a crucial role in regulating leukocyte functions, such as activation, proliferation, differentiation, migration, and immune function [1]. The inhibitory signal of CD300a depends on the phosphorylation of tyrosine residues in its cytoplasmic tail's immunoreceptor tyrosine-based inhibitory motifs (ITIMs) [4].

In mouse models, CD300a deficiency led to ameliorated neurological deficit after middle cerebral artery occlusion (MCAO) as it enhanced efferocytosis by infiltrating myeloid cells and reduced inflammation in the penumbral region [2]. In allergic inflammation, absence of CD300a in mice resulted in increased inflammatory features and changes in macrophage functionality, with CD300a-/-macrophages showing increased sensitivity to activation and altered cytokine release [3]. Blocking CD300a in Leishmania-infected mice enhanced the early clearance of parasites from visceral organs by modulating the effector functions of phagocytic and antigen-experienced T cells [5]. In a murine model of gout, CD300a-/-mice had persistent neutrophil influx and greater tissue damage, indicating its role in controlling neutrophil apoptosis and resolving articular inflammation [6].

In conclusion, CD300a is a key regulator of immune cell functions. Mouse models with CD300a deficiency have revealed its importance in various disease conditions, including ischemic stroke, allergic inflammation, Leishmania infection, and gout. These findings suggest that CD300a could be a potential target for immunotherapy in treating these diseases.

References:

1. Cao, Yue, Ao, Tianrang, Wang, Xiaohong, Fan, Jun, Tian, Xiaohong. 2021. CD300a and CD300f molecules regulate the function of leukocytes. In International immunopharmacology, 93, 107373. doi:10.1016/j.intimp.2021.107373. https://pubmed.ncbi.nlm.nih.gov/33548578/

2. Nakahashi-Oda, Chigusa, Fujiyama, Satoshi, Nakazawa, Yuta, Abe, Fumie, Shibuya, Akira. 2021. CD300a blockade enhances efferocytosis by infiltrating myeloid cells and ameliorates neuronal deficit after ischemic stroke. In Science immunology, 6, eabe7915. doi:10.1126/sciimmunol.abe7915. https://pubmed.ncbi.nlm.nih.gov/34652960/

3. Puzzovio, Pier Giorgio, Levy, Bruce D, Levi-Schaffer, Francesca. 2023. CD300a Regulates Mouse Macrophage Functionality in Allergic Inflammation. In International archives of allergy and immunology, 184, 720-726. doi:10.1159/000529606. https://pubmed.ncbi.nlm.nih.gov/36928079/

4. Zenarruzabeitia, Olatz, Vitallé, Joana, Eguizabal, Cristina, Simhadri, Venkateswara R, Borrego, Francisco. . The Biology and Disease Relevance of CD300a, an Inhibitory Receptor for Phosphatidylserine and Phosphatidylethanolamine. In Journal of immunology (Baltimore, Md. : 1950), 194, 5053-60. doi:10.4049/jimmunol.1500304. https://pubmed.ncbi.nlm.nih.gov/25980030/

5. Singh, Rajan, Anand, Anshul, Rawat, Arun K, Das, Pradeep, Singh, Rakesh K. 2022. CD300a Receptor Blocking Enhances Early Clearance of Leishmania donovani From Its Mammalian Host Through Modulation of Effector Functions of Phagocytic and Antigen Experienced T Cells. In Frontiers in immunology, 12, 793611. doi:10.3389/fimmu.2021.793611. https://pubmed.ncbi.nlm.nih.gov/35116028/

6. Valiate, Bruno V S, Queiroz-Junior, Celso M, Levi-Schaffer, Francesca, Galvão, Izabela, Teixeira, Mauro M. 2021. CD300a contributes to the resolution of articular inflammation triggered by MSU crystals by controlling neutrophil apoptosis. In Immunology, 164, 305-317. doi:10.1111/imm.13371. https://pubmed.ncbi.nlm.nih.gov/34002852/