Basic Information
Description
Leukocyte Ig-like receptors (LIRs) are a family of immunoreceptors expressed predominantly on monocytes and B cells and at lower levels on dendritic cells and natural killer (NK) cells. All members of LIR subfamily B, contain a cytoplasmic immunoreceptor tyrosine-based inhibitory motif (ITIM) and have an inhibitory function. Upon engagement of members of LIR subfamily B by MHC class I or other ligands and tyrosine phosphorylation of the ITIM, intracellular protein-tyrosine phosphatases, such as SHP1, are recruited and an inhibitory signal cascade ensues. It is thought to control inflammatory responses and cytotoxicity to help focus the immune response and limit autoreactivity. A subset of LILRB2 antagonism altered AKT-dependent maturation of macrophages in response to M-CSF, and enhanced NF-κB and STAT1 activation in response to LPS/IFN-γ stimuli. LILRB2 antagonism also rendered macrophages resistant to humoral cytokine-dependent STAT6 activation by IL-4, relieved the suppressive effect of macrophages on T cell proliferation, and reprogrammed human macrophages from A549 lung tumor models and primary human non–small cell lung carcinoma. Blockade of LILRB2 can be used to reprogram TAMs to improve the therapeutic outcome of cancer immune therapies through modulation of the tumor microenvironment. LILRB3 (ILT5/LIR3/CD85a), containing 4 extracellular Ig-like domains and 4 cytoplasmic ITIMs, represents an attractive immunomodulatory target because of its relative restriction to, and high expression on, myeloid cells. LILRB3 activation confers potent immunoinhibitory functions through reprograming and tolerizing of myeloid cells and suggest that modulating LILRB3 activity may provide exciting new treatment strategies in various disease settings, such as transplantation.
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Details
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Protein expression analysis (F2)
Strain specific LILRB2 expression analysis in transgenic B-Tg(hLILRB2-hLILRB3) mice by flow cytometry. Granulocytes of blood were collected from wild-type mice (+/+) and transgenic B-Tg(hLILRB2-hLILRB3) mice (Tg), and analyzed by flow cytometry with species-specific anti-human LILRB2 antibody. Human LILRB2 was detectable in granulocytes from B-Tg(hLILRB2-hLILRB3) mice but not wild-type mice.
Strain specific LILRB2 expression analysis in transgenic B-Tg(hLILRB2-hLILRB3) mice by flow cytometry. Dendritic cells derived from bone marrow were collected from wild-type mice (+/+) and transgenic B-Tg(hLILRB2-hLILRB3) mice (Tg), and analyzed by flow cytometry with species-specific anti-human LILRB2 antibody. Human LILRB2 was detectable in dendritic cells from B-Tg(hLILRB2-hLILRB3) mice but not in wild-type mice.
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Summary
LILRB2 protein expression:
1.Detectable in dendritic cells derived from bone marrow. (F2)
2.Detectable in blood cells. (F2)
3.Detectable in B cells, dendritic cells and macrophages from blood. (F3)
LILRB3 protein expression:
1.Detectable in dendritic cells derived from bone marrow. (F2)
2.Detectable in T cells, B cells, dendritic cells and macrophages from blood. (F3)
