Leukocyte immunoglobulin-like receptor subfamily B member 2 and Leukocyte immunoglobulin-like receptor subfamily B member 4 (LILRB2 and LILRB4) (LILRB2/LILRB4)

Leukocyte immunoglobulin-like receptor subfamily B member 2 (LILRB2/ILT4) and member 4 (LILRB4/ILT3) are critical inhibitory receptors primarily expressed on myeloid lineage cells, including monocytes, macrophages, and dendritic cells (NIH, 2024). These receptors function as 'myeloid checkpoints' by transmitting inhibitory signals through cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs) upon binding to ligands such as HLA-G, APOE, and fibronectin (PubMed, 2023). In the tumor microenvironment, their upregulation promotes an immunosuppressive state by inducing M2-like macrophage polarization, enhancing the activity of myeloid-derived suppressor cells (MDSCs), and inhibiting T cell activation and proliferation (Nature Immunology, 2002; NIH, 2018). Therapeutic strategies targeting these receptors, such as monoclonal antibodies like MK-4830 and NGM707, aim to block these inhibitory interactions to reprogram the immune environment from suppressive to stimulatory, thereby enhancing antitumor immunity (Immune-Onc, 2024). Beyond oncology, these receptors play significant roles in maintaining peripheral tolerance and are implicated in the pathogenesis of autoimmune diseases and the induction of transplant tolerance (ASH Publications, 2025).

Other names

ILT3ILT4CD85kCD85dLIR-2LIR-5Immunoglobulin-like transcript 3Immunoglobulin-like transcript 4LILRB2LILRB4Leukocyte immunoglobulin-like receptor subfamily B member 2Leukocyte immunoglobulin-like receptor subfamily B member 4

Antagonism of inhibitory signaling by blocking the binding of immunosuppressive ligands (e.g., HLA-G, APOE) to LILRB2 and LILRB4, preventing ITIM-mediated recruitment of SHP-1/2 phosphatases and restoring the proinflammatory activity of myeloid cells and T cells (NIH, 2024; PubMed, 2023).