Disease relevance of LILRB4

• The two extracellular immunoglobulin domains of LIR-5 were expressed in Escherichia coli to a high level and were found to accumulate in inclusion bodies [1].

High impact information on LILRB4

• We have identified two cell subsets in human blood based on the lack of lineage markers (lin-) and the differential expression of immunoglobulin-like transcript receptor 1 (ILT1) and ILT3 [2].
• Tolerization of dendritic cells by T(S) cells: the crucial role of inhibitory receptors ILT3 and ILT4 [3].
• Immunoglobulin-like transcript 3 (ILT3) and ILT4 belong to a family of inhibitory receptors expressed by human monocytes and dendritic cells [3].
• A novel inhibitory receptor (ILT3) expressed on monocytes, macrophages, and dendritic cells involved in antigen processing [4].
• Signal extinction involves SH2-containing protein tyrosine phosphatase 1, which is recruited by ILT3 upon cross-linking [4].

Chemical compound and disease context of LILRB4

• The MICs of cefotaxime were higher for E. coli ILT-1 and K. pneumoniae ILT-2 than for K. pneumoniae ILT-3, while the opposite was found for the MICs of ceftazidime [5].

Biological context of LILRB4

• ILT3 and KIRCI were in the same head-to-tail orientation as has been described for other KIR loci which may facilitate addition or loss of genes between different haplotypes [6].
• 5' rapid amplification of cDNA ends defined the putative transcription initiation site of the LIR-5 gene, which is TATA-less [7].
• Studies of human heart transplant recipients showed that rejection-free patients have circulating TS cells, which induce the up-regulation of ILT3 and ILT4 in donor APCs [3].
• Indeed, co-ligation of ILT3 to stimulatory receptors expressed by APCs results in a dramatic blunting of the increased [Ca2+]i and tyrosine phosphorylation triggered by these receptors [4].
• The gene encoding HM18, in common with the genes for the human Fc receptor for IgA and the human NK cell inhibitory receptors, was localized to chromosome 19q13 [8].

Anatomical context of LILRB4

• Successful prokaryotic generation of correctly folded LIR-5 in high levels has implications for production of other LRC receptors and should greatly facilitate attempts to define the structure and ligands of this important regulator of dendritic cell function [1].
• In contrast, addition of soluble ILT3 or overexpression of ILT3 in cocultures significantly reduced T cell proliferation [9].
• IL-10 inhibits endothelium-dependent T cell costimulation by up-regulation of ILT3/4 in human vascular endothelial cells [9].
• Tolerogenic antigen presenting cells (APC) are characterized by high expression of the inhibitory receptors ILT3 and ILT4 [10].
• We have engineered ILT3 and ILT4 cytoplasmic deletion mutants (ILT3delta and ILT4delta), which were transfected in the dendritic-like cell line KG1, to investigate ILT3 and ILT4's capacity to signal extracellularly [10].

Associations of LILRB4 with chemical compounds

• The 1.6-kbp cDNA, HM18, predicts a 49-kDa type 1 integral membrane protein that, like mouse gp49B1, contains two extracellular C2 type Ig superfamily domains and two consensus immunoreceptor tyrosine-based inhibition motifs in the cytoplasmic domain [8].
• Here we show an in vivo correlate of the increased ILT3 expression on DCs in healing psoriatic lesions following topical treatment with the 1,25(OH)(2)D(3) analog calcipotriol [11].

Regulatory relationships of LILRB4

• Blocking ILT-3 or IL-12 does not diminish the capacity of these DCs to induce regulation or Foxp3 expression on the regulatory T cells [12].

Other interactions of LILRB4

• In conclusion, the T cell costimulatory potential of human EC is markedly suppressed by IL-10 due to up-regulation of ILT3/ILT4, obviously not involving generation of Treg [9].
• We also showed that Pg.LPS enhanced the tolerogenic properties of APCs and up-regulated ILT-3 and B7-H1 expression [13].

Analytical, diagnostic and therapeutic context of LILRB4

• Using a polymerase chain reaction (PCR)-based approach, we now demonstrate by cell fractionation and sequencing studies that ILT3 precursor RNA is expressed and retained in nuclei of resting EC [14].
• Western blot analysis showed that the expression of the mature ILT3 transcript is accompanied by production of ILT3 protein [14].

References