LAIR1

LAIR1, or leukocyte-associated immunoglobulin-like receptor 1 (CD305), is an inhibitory receptor of the immunoglobulin superfamily expressed on a broad range of leukocytes, including natural killer cells, T cells, B cells, monocytes, dendritic cells, and platelets. It is a type I transmembrane protein with two extracellular immunoglobulin-like domains and a cytoplasmic tail that contains two immunoreceptor tyrosine-based inhibition motifs (ITIMs).

Signal transduction through LAIR1 involves ligand binding, phosphorylation of the ITIMs, and recruitment of phosphatases such as SHP-1 and SHP-2. This signaling suppresses activating pathways, reducing processes such as cytokine production, degranulation, and cellular proliferation, thereby tempering immune responses.

The principal ligand for LAIR1 is collagens, particularly types I to III, with binding contributing to inhibitory signals that help maintain tissue homeostasis and tolerance in collagen-rich environments. Additional interactions with other extracellular matrix components have been described, but collagen is the primary canonical ligand.

LAIR1 functions as an immune checkpoint that modulates activation and prevents excessive inflammation. By dampening immune cell responses, it can influence outcomes in contexts such as autoimmunity, fibrosis, and cancer. A soluble homolog, LAIR-2, can bind collagen and act as a decoy receptor, potentially modulating LAIR1 signaling by competing for ligand binding.

In research and clinical contexts, LAIR1 is studied for its role in regulating immune responses and its potential as a therapeutic target or biomarker in autoimmune diseases, fibrotic conditions, and cancer. The LAIR1 gene is conserved across mammals and part of a broader LAIR gene family involved in immune regulation.