LILRB4
Description
The LILRB4 (leukocyte immunoglobulin like receptor B4) is a protein-coding gene located on chromosome 19.
LILRB4, encoded by the LILRB4 gene, is a member of the leukocyte immunoglobulin-like receptor (LIR) family, located on chromosome 19q13.4. This protein belongs to the subfamily B class of LIR receptors, characterized by two or four extracellular immunoglobulin domains, a transmembrane domain, and two to four cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs). Expressed on monocytic cells, LILRB4 transduces a negative signal, inhibiting immune response stimulation. It also plays a role in antigen capture and presentation. LILRB4 is thought to control inflammatory responses and cytotoxicity, helping focus and limit autoreactivity in the immune system. It is a potential target for tumor immunotherapy, as it is expressed on tumor-associated macrophages and negatively regulates the immune response within tumors. The expression of LILRB4 on monocytic myeloid leukemia cells supports infiltration and inhibits T cell proliferation. Multiple transcript variants encoding different isoforms have been found for this gene.
LILRB4 is an inhibitory receptor that plays a critical role in regulating immune responses and maintaining immune tolerance. It binds to various ligands, including FN1, APOE, and ALCAM/CD166, and inhibits receptor-mediated phosphorylation of cellular proteins and intracellular calcium ion mobilization. LILRB4 also inhibits FCGR1A/CD64-mediated monocyte activation, at least partially through binding to FN1, by downregulating the phosphorylation of several proteins (LCK, SYK, LAT, and ERK), leading to reduced TNF production. Furthermore, it suppresses T cell proliferation, induces anergy, inhibits the differentiation of IFNG-producing CD8+ cytotoxic T cells, and promotes the generation of CD8+ T suppressor cells. LILRB4 also upregulates CD86 expression on dendritic cells, interferes with TNFRSF5 signaling and NF-kappa-B upregulation, and interacts with PTPN6.
LILRB4 is also known as B4, CD85K, ILT-3, ILT3, LIR-5, LIR5.
Associated Diseases
- Brugada syndrome
- common variable immunodeficiency
- severe combined immunodeficiency due to CARD11 deficiency
- familial atrial fibrillation
- neutrophil immunodeficiency syndrome
- isolated agammaglobulinemia
- severe combined immunodeficiency due to CTPS1 deficiency
- immunodeficiency 18
- combined immunodeficiency with skin granulomas
