CSF2RB

Official Full Name

colony stimulating factor 2 receptor subunit beta

Organism

Homo sapiens

GeneID

1439

Background

The protein encoded by this gene is the common beta chain of the high affinity receptor for IL-3, IL-5 and CSF. Defects in this gene have been reported to be associated with protein alveolar proteinosis (PAP). [provided by RefSeq, Jul 2008]

Synonyms

CD131; IL3RB; IL5RB; SMDP5; CDw131; betaGMR;

Bio Chemical Class

Cytokine receptor

Protein Sequence

MVLAQGLLSMALLALCWERSLAGAEETIPLQTLRCYNDYTSHITCRWADTQDAQRLVNVTLIRRVNEDLLEPVSCDLSDDMPWSACPHPRCVPRRCVIPCQSFVVTDVDYFSFQPDRPLGTRLTVTLTQHVQPPEPRDLQISTDQDHFLLTWSVALGSPQSHWLSPGDLEFEVVYKRLQDSWEDAAILLSNTSQATLGPEHLMPSSTYVARVRTRLAPGSRLSGRPSKWSPEVCWDSQPGDEAQPQNLECFFDGAAVLSCSWEVRKEVASSVSFGLFYKPSPDAGEEECSPVLREGLGSLHTRHHCQIPVPDPATHGQYIVSVQPRRAEKHIKSSVNIQMAPPSLNVTKDGDSYSLRWETMKMRYEHIDHTFEIQYRKDTATWKDSKTETLQNAHSMALPALEPSTRYWARVRVRTSRTGYNGIWSEWSEARSWDTESVLPMWVLALIVIFLTIAVLLALRFCGIYGYRLRRKWEEKIPNPSKSHLFQNGSAELWPPGSMSAFTSGSPPHQGPWGSRFPELEGVFPVGFGDSEVSPLTIEDPKHVCDPPSGPDTTPAASDLPTEQPPSPQPGPPAASHTPEKQASSFDFNGPYLGPPHSRSLPDILGQPEPPQEGGSQKSPPPGSLEYLCLPAGGQVQLVPLAQAMGPGQAVEVERRPSQGAAGSPSLESGGGPAPPALGPRVGGQDQKDSPVAIPMSSGDTEDPGVASGYVSSADLVFTPNSGASSVSLVPSLGLPSDQTPSLCPGLASGPPGAPGPVKSGFEGYVELPPIEGRSPRSPRNNPVPPEAKSPVLNPGERPADVSPTSPQPEGLLVLQQVGDYCFLPGLGPGPLSLRSKPSSPGPGPEIKNLDQAFQVKKPPGQAVPQVPVIQLFKALKQQDYLSLPPWEVNKPGEVC

Open

Disease

Acute myeloid leukaemia, Asthma, Immune system disease, Multiple myeloma, Myeloproliferative neoplasm

Approved Drug

Clinical Trial Drug

5 +

Discontinued Drug

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Detailed Information

Common beta chain for high-affinity receptors of IL-3, IL-5, and Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF), the CSF2RB gene generates a protein. GM-CSF is a multifarious cytokine with important involvement in immunological responses, hematopoiesis, and many inflammatory disorders. Particularly lung illnesses like pulmonary alveolar proteinosis (PAP), and defects in the CSF2RB gene are linked to numerous clinical situations. To generate heterodimeric complexes activating similar signaling pathways, CSF2RB interacts with other receptor subunits (e.g., IL3RA, IL5RA, and CSF2RA). These channels include not only immune cell activation but also blood system hematopoietic precursor cell differentiation.

Immunological Functions of GM-CSF

GM-CSF is a crucial pro-inflammatory agent that not only helps the immune system but also performs major roles in many physiological and pathogenic mechanisms. It controls macrophage, dendritic cells (DC), eosinophils, and neutrophil production and differentiation by binding to certain receptors.

Normal conditions allow GM-CSF to be almost invisible in the blood of healthy people. But during immunological reactions, it is released by different cells—e.g., T cells, mast cells, endothelium cells—and acts on myeloid cells via their receptors. By affecting the release of cytokines including IL-1, IL-6, and TNF, GM-CSF alters immune responses and stimulates inflammation. GM-CSF controls immune cell recruitment and polarization in inflammatory conditions including the lungs and intestines thereby enabling their movement to afflicted sites.

GM-CSF's Relationship with Diseases

Different Particularly inflammatory and autoimmune illnesses, GM-CSF expression is intimately linked to several disorders. Maintenance of alveolar macrophage homeostasis and activity in the lungs depends on GM-CSF. PAP and a higher risk of lung infections may result from GM-CSF expression either being inhibited or deficient. GM-CSF also participates in a number of prevalent clinical inflammatory diseases including Graft-versus-Host Disease (GVHD), Cytokine Release Syndrome (CRS), and Acute Respiratory Distress Syndrome (ARS).

In inflammatory settings, GM-CSF not only stimulates the multiplication and mobility of inflammatory cells but also creates a positive feedback loop via immune cell contacts, therefore sustaining chronic inflammation. Increased immune responses and too high cytokine production aggravate tissue damage even more, therefore starting a vicious cycle.

GM-CSF's Role in Different Immune Cells

1. Monocytes: GM-CSF regulates monocyte function by inducing them to adopt a pro-inflammatory phenotype, especially in chronic inflammatory or autoimmune diseases, enhancing local and systemic inflammatory responses.

Figure 1 depicts the downstream signaling of the GM-CSF receptor in myeloid cells, where GM-CSF binding triggers receptor dimerization, leading to JAK2-mediated signaling pathways that regulate cell survival and proliferation. Figure 1. Signaling downstream of the GM-CSF receptor in myeloid cells. (Kumar A, et al., 2022)

2. Macrophages: A main target for GM-CSF, macrophages depend on it for correct development and operation. Maintaining functional alveolar macrophages requires GM-CSF, which is also vital under other circumstances. A lack of the GM-CSF receptor may cause alveolar proteins to build up, which would cause macrophage malfunction and greatly damage the immune system's capacity to fight against infections. Furthermore under control by GM-CSF are macrophage activation and cytokine release, which can aggravate tissue damage in affected locations.

3. Dendritic Cells: GM-CSF is very essential for the development of dendritic cells (DCs). GM-CSF not only boosts macrophage activity but also alters dendritic cell operations during inflammation and immunological responses. It plays a vital part in coordinating immune activation and response as it stimulates Th2 and Th17 immune responses, helps immune cells to be recruited to inflamed regions, and improves antigen presentation.

4. Eosinophils: Eosinophil migration and function depend on GM-CSF. Higher GM-CSF levels are tightly linked to increased eosinophil activity in chronic allergic diseases such as asthma, which fuels inflammation and disease advancement. GM-CSF stimulates eosinophil migration to affect allergic-related processes and may aggravate tissue damage.

5. Neutrophils: GM-CSF is essential for controlling their generation and mobilization; they are front-line fighters against infections. It improves the fight against infections capacity of the immune system. In chronic inflammatory illnesses, however, GM-CSF may cause too high neutrophil buildup, which usually aggravates tissue damage at the relevant locations.

GM-CSF's Role in Cancer

GM-CSF's contribution to the cancer immune microenvironment is multifarious and complicated. On one side, it strengthens immune system assaults on tumor cells, thus promoting anticancer effects by activating dendritic cells and macrophages and so increasing T cell-mediated immunity. Conversely, in other malignancies like colorectal cancer, higher GM-CSF expression is linked to worse clinical prognosis and more tumor invasiveness.

Investigating GM-CSF's processes in different tumors using this cytokine's immunostimulating qualities might help to develop new immunotherapeutic approaches. GM-CSF is attracting more and more interest as a viable therapeutic target even though its promise in immunotherapy is still under assessment.

References:

Kumar A, Taghi Khani A, et al. GM-CSF: A Double-Edged Sword in Cancer Immunotherapy. Front Immunol. 2022 Jul 5;13:901277.
Hansen PJ, Dobbs KB, et al. Programming of the preimplantation embryo by the embryokine colony stimulating factor 2. Anim Reprod Sci. 2014 Sep;149(1-2):59-66.

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