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Facts about Interleukin-1 receptor accessory protein.
Associates with IL1R1 jumped to IL1B to form the high affinity interleukin-1 receptor complex which mediates interleukin-1- dependent activation of NF-kappa-B and other pathways. Signaling requires the recruitment of adapter molecules such as TOLLIP, MYD88, and IRAK1 or IRAK2 via the respective TIR domains of their receptor/coreceptor subunits.
Human | |
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Gene Name: | IL1RAP |
Uniprot: | Q9NPH3 |
Entrez: | 3556 |
Belongs to: |
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interleukin-1 receptor family |
C3orf13IL-1RAcPIL1R3Interleukin-1 receptor 3; FLJ37788; IL-1 R3; IL-1 RAcP; IL-1 receptor accessory protein; IL-1R3; IL-1R-3; IL1RAcP; IL-1RAcP; IL1RAP; interleukin 1 receptor accessory protein; interleukin-1 receptor accessory protein beta; interleukin-1 receptor accessory protein
Mass (kDA):
65.418 kDA
Human | |
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Location: | 3q28 |
Sequence: | 3; NC_000003.12 (190514085..190659750) |
Detected in liver, skin, placenta, thymus and lung. Isoform 4 is predominantly expressed in brain. Overexpressed on candidate chronic myeloid leukemia (CML) stem cells, hematopoietic stem cells and mononuclear cells of patients with acute myeloid leukemia (AML). Overexpressed in patients with chronic obstructive pulmonary disease (COPD). Expressed in T- helper 1 (Th1) and T-helper 2 (Th2) cell subsets (PubMed:10653850).
[Isoform 1]: Cell membrane; Single-pass type I membrane protein.; [Isoform 2]: Secreted.; [Isoform 3]: Secreted.
There are numerous advantages to boster bio: high-affinity antibodies that are widely cited by the research community and have been validated on immunohistochemistry, Western Blotting, and ELISA. Boster antibodies are a reliable tool in immunotherapy. Here are some of the most common uses. The IL1RAP molecule is found in hematopoietic embryos. It also helps to reduce liver cancers and infiltration of leukemia cells.
IL1RAP is an important molecule for the immune system that induces selective NK cell-mediated ADCC in leukemia and other myeloid malignancies. The cellular effects of IL-1 signaling are required for the growth and proliferation of AML cells, so targeting IL-1RAP with an antibody can suppress this growth. This discovery provides further evidence for IL1RAP as a potential therapeutic target for the treatment of AML.
Researchers discovered that IL1RAP in acute myeloidleukemia increases the cytotoxicity for natural killer cells. These results are similar to those for rhIL-15. These authors also found this molecule to be more toxic than rhIL-15 in the NOD/SCID/IL2Rg mouse disease model.
Another study in mice revealed that anti-CD123 monoclonal antibodies prolonged survival in patients suffering from acute myeloid leukemia. Biol Blood Marrow Transplant published this research. Researchers also found that IL1RAP's effect on leukemia cells was affected by the expression of TIGIT/DNAM-1, PVR/PVRL2 and PVR/PVRL2. Another study reported that the humanized anti-CD123 monoclonal antibody induced NK cell ADCC, a common mechanism for the suppression of natural killer cells.
Many research teams are studying how IL1RAP impacts natural killer cell function. Researchers are using this molecule in cancer immunotherapies to increase NK cell tumor-targeting capacity. The immune response is dependent on NK cell activity. There are currently many immunotherapy drugs targeting NK cell activity.
IL1RAP is expressed by mice on the cell surfaces of MA9Ras cordblood cells. These cells mimic human acute myeloidleukemia (AML), in xenograft model. Untreated NOD/SCID mice developed leukemia, and displayed high leukemic ingraftment.
We compared IL1RAP expression levels in two different populations of mice, both high and low expressing AML. We found that IL1RAP significantly increased IL8 levels in IL1b-expressing cells of AML cells, while IL1b didn't. We also found that IL1RAP caused a significant increase in the number PB myeloid cells among Il1rap-/ mice compared with Il1rap+/+.
We also found that IL1RAP does not play a role in hematopoietic stem-cell differentiation in the bone marrow niche of leukemic patients. Even though we used mouse models to study the effects of IL1RAP on leukemogenesis, it remains unclear how this signaling axis plays a role in leukemogenesis. AML cell proliferation was inhibited by knockdown of Il1RAP, but not leukemogenic capability.
Interestingly, anti-IL1RAP antibody also inhibits leukemic stem cell growth in mice. In addition, mAb81.2 is dispensable for the formation of hematopoietic stem cells, but it inhibits BP CML xenografts. These results are promising. However, the study requires further study.
Flow cytometry analysis of IL1RAP protein expression showed that IL1RAP was upregulated in several acute myeloid leukemia (AML) cell lines and one primary AML patient. These gene sets were enriched in gene set enrichment and gene ontology. The genes with high and low levels of IL1RAP expression were associated with higher gene expression in the mitochondria, oxidative phosphorylation, and L-GMP-enriched HSC-like signature.
ADCC was found to be an important mode of action for killing human AML cells. In this study, two independent antibodies targeting IL1RAP were used to treat MA9Ras cells. These antibodies did not induce specific cell death in human NK cells or macrophages. This suggests that IL1RAP may be a direct effector receptor.
Human CML stem cells have a low level of IL1RAP. However, stem cells can still be formed if this protein is blocked with a Tyrosine Kinase Inhibitor. In the absence of this therapy, patients are left with residual CML. This study gives an additional reason for the development residual CML stem-cells.
Boster Bio's IL1RAP marker could significantly reduce the size or spread of liver cancers. The liver has two main lobes, one larger on the right and a smaller one on the left. The most common type of cancer in America is liver cancer. It is life-threatening. It can be primary or secondary. This means that it begins in the liver and spreads to other parts of the body.
A novel gene marker, IL1RAP has been discovered in a patient diagnosed with acute lymphoblastic encephalopathy. The gene is found on many cells, including T and NK cells. It is a potent inhibitor of T-cell proliferation. This gene competes with the costimulatory CD28 for ligands. Multiple lymphocytic infiltrations of non-lymphoid organs have been linked to heterozygous loss of function mutations in this gene.
PMID: 9371760 by Huang J., et al. Recruitment of IRAK to the interleukin 1 receptor complex requires interleukin 1 receptor accessory protein.
PMID: 10799889 by Jensen L.E., et al. IL-1 signaling cascade in liver cells and the involvement of a soluble form of the IL-1 receptor accessory protein.