LILRA1

LILRA1 (Leukocyte Immunoglobulin-Like Receptor A1), also known as ILT1 (Immunoglobulin-Like Transcript 1) and CD85a, is a protein encoded by the LILRA1 gene in humans. It belongs to the leukocyte immunoglobulin-like receptor (LILR) family, which are a group of transmembrane glycoproteins expressed primarily on immune cells, including monocytes, macrophages, dendritic cells, neutrophils, B cells, and some T cells.

LILRA1 functions as an inhibitory receptor. Its extracellular domain contains four immunoglobulin-like domains, which bind to classical and non-classical HLA class I molecules (MHC class I). Engagement of LILRA1 by HLA class I molecules on target cells delivers an inhibitory signal into the immune cell. This inhibitory signal is transduced via immunoreceptor tyrosine-based inhibition motifs (ITIMs) located in its cytoplasmic tail, leading to the recruitment of phosphatases such as SHP-1 and SHP-2. These phosphatases dephosphorylate signaling molecules involved in immune cell activation, thereby suppressing immune responses.

The binding of LILRA1 to HLA class I molecules has important implications for immune regulation. By interacting with HLA-G, a non-classical HLA class I molecule with restricted tissue expression, LILRA1 plays a role in maternal-fetal tolerance at the maternal-fetal interface, preventing the mother's immune system from rejecting the fetus. It also contributes to the regulation of inflammatory responses, preventing excessive inflammation and tissue damage in autoimmune diseases and chronic infections.

Genetic polymorphisms in the LILRA1 gene have been associated with susceptibility to various diseases, including autoimmune disorders, viral infections, and cancer. These associations suggest that variations in LILRA1 expression or function can influence immune responses and disease outcomes.

In summary, LILRA1 is an inhibitory receptor that plays a crucial role in regulating immune cell function by interacting with HLA class I molecules and delivering inhibitory signals. Its involvement in maternal-fetal tolerance and the regulation of inflammation highlights its importance in maintaining immune homeostasis and preventing immune-mediated diseases.