
-   In malignancies, tumor cells secrete IL-6 and IL-10 to induce tDCs with high expression of LILRB4, which attenuates the response of T cells to tumor-associated antigens. LILRB4 may induce tolerance of DCs to promote immunological tolerance in autoimmune diseases [PMID: 20132030].
-   In non-small-cell lung cancer (NSCLC), LILRB4 is activated by APOE binding and further recruits SHP-2 and SHIP-1 to activate ERK1/2 signaling and increase the expression of vascular endothelial growth factor (VEGF) to promote cell motility, angiogenesis, and cancer metastasis.[PMID: 33152402].
-   LILRB4 signalling in leukaemia cells mediates T cell suppression and tumour infiltration. In AML, apolipoprotein E (APOE) binds to LILRB4, in turn recruiting SHP-2 to the intracellular ITIMs of LILRB4, which further activates the NFkappaB signaling pathway to promote leukemia cell infiltration via the urokinase receptor (uPAR) and inhibit T cell activation via ARG-1 [PMID: 30333625]. LILRB4 expression is upregulated by protein arginine methyltransferase 5 (PRMT5) in AML cells, which results in activation of the mTOR pathway to enhance the invasion ability of AML cells [PMID: 34712735].

## Summary

The leukocyte immunoglobulin-like receptor 4 (LILRB4), encoded by the Lilrb4 gene, functions as an inhibitory receptor involved in the down-regulation of the immune response and the development of immune tolerance [CS: 9]. It inhibits monocyte activation, T cell proliferation, induces anergy, and suppresses differentiation of IFNgamma-producing CD8+ cytotoxic T cells [CS: 8]. Additionally, LILRB4 modulates immune responses by inducing the generation of CD8+ T suppressor cells and up-regulating CD86 on dendritic cells [CS: 7].

In the brain, during conditions of disease or toxicity, LILRB4 expression is upregulated [CS: 6]. For instance, in Alzheimer's disease, its increased expression in microglia around plaques suggests a response to inflammatory conditions [CS: 6]. This upregulation is likely a mechanism to control excessive immune responses and limit neuroinflammation [CS: 7]. By dampening the activation of microglia and other immune cells in the brain, LILRB4 helps to prevent further damage that could be caused by an overactive immune response, thus potentially protecting neural tissues [CS: 6]. In the context of aging and diseases like amyotrophic lateral sclerosis, the increased expression of Lilrb4 in microglia may serve a similar function, acting to mitigate chronic inflammatory responses and maintain a balance in the brain's immune environment [CS: 5]. This response can be seen as a protective measure against the detrimental effects of prolonged inflammation and immune activation in the brain, which are characteristic of various neurodegenerative conditions [CS: 6].
