Leukocyte immunoglobulin-like receptors ILT3 and ILT4 (ILT3 and ILT4)

ILT3 (LILRB4) and ILT4 (LILRB2) are immunoglobulin-like inhibitory receptors highly expressed on dendritic cells, monocytes, and macrophages. They are critical regulators of immune homeostasis, promoting tolerance by inhibiting antigen presentation and suppressing T cell activation. Both play major roles in creating tolerogenic states in cancer, transplantation, and chronic inflammatory diseases. Their ligands include HLA class I molecules, notably HLA-G for ILT4, which drive signaling cascades involving ITIM motifs, SHP phosphatases, and the IL-6–STAT3 pathway. Recent research indicates that these receptors are involved in immune evasion by tumors and are promising therapeutic targets. Antagonists of ILT3 and ILT4 are being developed to enhance anti-tumor immune responses. However, clinical translation requires careful management due to their role in self-tolerance and risk of autoimmunity.

Other names

LILRB4LIR-5CD85kLILRB2LIR-2CD85d

Receptor blockade: antibody antagonists can inhibit immunosuppressive function and restore T cell activity. Modulation of dendritic cell and myeloid regulatory cell phenotype (promoting maturation, reducing suppressive cytokines such as IL-10). Disruption of ITIM motif-mediated inhibitory signaling.