CD300A molecule | Elisa - Clia - Antibody - Protein

Background

CD300A, also known as immune receptor expressed by myeloid cells (IREM-1) or leukocyte mono-immunoglobulin-like receptor 8 (LMIR8), is a member of the CD300 family of immunoreceptors. This molecule plays a significant role in the regulation of immune responses. It is encoded by the CD300A gene located on the human chromosome 17. CD300A is primarily expressed on the surface of myeloid cells, including monocytes, macrophages, dendritic cells, and some subsets of lymphocytes.

The CD300 family consists of several members, each contributing to the regulation of immune cell functions. CD300A, in particular, is recognized for its inhibitory functions, helping to maintain immune homeostasis and preventing overactivation that could lead to autoimmunity.

Protein Structure

CD300A is a type I transmembrane protein characterized by an extracellular domain, a transmembrane region, and a cytoplasmic tail:

• Extracellular Domain: The extracellular part of CD300A consists of a single immunoglobulin (Ig)-like domain. This domain is responsible for ligand binding and is crucial for the receptor's function in immune regulation.
• Transmembrane Region: The transmembrane region anchors the protein in the cell membrane. It is relatively hydrophobic and allows the protein to span the lipid bilayer of the cell membrane.
• Cytoplasmic Tail: The cytoplasmic tail of CD300A contains immunoreceptor tyrosine-based inhibitory motifs (ITIMs). These ITIMs are critical for the inhibitory signaling pathways mediated by CD300A. Upon ligand binding, the ITIMs are phosphorylated, recruiting phosphatases such as SHP-1 and SHP-2, which downregulate activating signaling pathways.

Classification and Subtypes

CD300A belongs to the CD300 family, which includes both activating and inhibitory receptors. The classification within this family is based on the presence of ITIMs or immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic tails.

• Inhibitory Receptors: These include CD300A, which contains ITIMs and delivers inhibitory signals to dampen immune responses.
• Activating Receptors: These contain ITAMs or associate with adaptor proteins that have ITAMs, delivering activating signals that promote immune cell activation.

Other members of the CD300 family include CD300B (activating receptor), CD300C, CD300D, CD300E, CD300F, and CD300G, each contributing differently to immune regulation.

Function and Biological Significance

CD300A is primarily involved in the negative regulation of immune responses. Its functions and biological significance include:

1. Inhibition of Immune Cell Activation: CD300A inhibits activation signals in myeloid cells. Upon ligand binding, the ITIMs in its cytoplasmic tail are phosphorylated, recruiting phosphatases like SHP-1 and SHP-2. These phosphatases dephosphorylate key signaling molecules, thereby inhibiting immune cell activation and preventing excessive inflammatory responses.
2. Maintenance of Immune Homeostasis: By providing inhibitory signals, CD300A helps maintain immune homeostasis. It ensures that immune responses are appropriately regulated, preventing the development of autoimmune diseases.
3. Regulation of Phagocytosis: CD300A negatively regulates phagocytosis in macrophages and dendritic cells. This function is crucial in controlling the clearance of apoptotic cells and maintaining tissue homeostasis.
4. Role in Allergic Responses: CD300A is expressed on eosinophils and mast cells, where it modulates allergic responses. Its inhibitory signals can reduce the release of pro-inflammatory mediators, thereby mitigating allergic reactions.
5. Interaction with Phospholipids: CD300A binds to phospholipids such as phosphatidylserine and phosphatidylethanolamine exposed on apoptotic cells. This binding plays a role in the recognition and clearance of dying cells, contributing to the resolution of inflammation.

Clinical Issues

CD300A is implicated in various clinical conditions, primarily due to its role in immune regulation:

1. Autoimmune Diseases: Dysregulation of CD300A expression or function can contribute to the development of autoimmune diseases. Insufficient inhibitory signaling can lead to overactive immune responses, damaging self-tissues.
2. Infectious Diseases: CD300A plays a role in the immune response to infections. Its inhibitory signals can modulate the activity of immune cells during infections, influencing the outcome of disease.
3. Allergic Conditions: Given its expression on eosinophils and mast cells, CD300A is involved in allergic diseases such as asthma and allergic rhinitis. Modulating CD300A activity could be a potential therapeutic strategy for managing allergic inflammation.
4. Cancer: The role of CD300A in cancer is complex. On one hand, its inhibitory signals can prevent excessive inflammation that might contribute to tumor growth. On the other hand, inhibiting immune responses could allow tumors to evade immune surveillance. Understanding this balance is crucial for developing CD300A-targeted therapies in oncology.

Summary

CD300A, a member of the CD300 family, is a key inhibitory receptor on myeloid cells. Its structure includes an extracellular Ig-like domain, a transmembrane region, and a cytoplasmic tail with ITIMs. CD300A plays crucial roles in regulating immune responses, maintaining homeostasis, and modulating inflammation and phagocytosis. It is involved in various clinical conditions, including autoimmune diseases, infections, allergies, and cancer. Understanding the precise mechanisms of CD300A's function and its interactions with other immune regulatory molecules is essential for developing targeted therapies that modulate immune responses in various diseases.