CSF2RB mediates immune responses through three key mechanisms:
Cytokine Signaling: Forms dodecameric complexes with ligand-specific α-chains (e.g., CSF2RA for GM-CSF) to activate JAK2/STAT5, PI3K/mTOR, and MEK/ERK pathways .
Immune Cell Survival: Promotes proliferation and differentiation of myeloid cells, dendritic cells, and macrophages .
Tumor Microenvironment Modulation: Low CSF2RB expression in lung adenocarcinoma (LUAD) correlates with poor survival (HR = 0.65, p < 0.05) and advanced tumor stages .
Biomarker Potential: Reduced CSF2RB expression in LUAD tumors predicts worse outcomes (5-year survival: 45% vs. 68% in high-expression groups) .
Immune Infiltration: Positively correlates with CD4+ T cells, macrophages, and NK cells in LUAD (r = 0.32–0.41) .
Therapeutic Target: Activating mutations (e.g., germline mutations in leukemia) drive ligand-independent STAT5 activation, suggesting druggable pathways .
Regulatory T Cells (Tregs): Overexpressed in Tregs of multiple sclerosis (MS) and systemic lupus erythematosus (SLE) patients compared to healthy controls (p ≤ 0.01) .
Genetic Variants: SNPs (rs5756405, rs5756391) linked to MS susceptibility alter GM-CSF/STAT5 signaling .
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine that plays a crucial role in the immune system by stimulating the production and function of white blood cells, particularly granulocytes and macrophages . GM-CSF is produced by various cell types, including T cells, B cells, macrophages, monocytes, mast cells, vascular endothelial cells, and fibroblasts .
The GM-CSF receptor is a heterodimer composed of two subunits: the alpha (α) subunit and the beta (β) subunit . The alpha subunit (GMRα) binds GM-CSF with low affinity, while the beta subunit (βc) is responsible for signal transduction and is shared with the receptors for interleukin-3 (IL-3) and interleukin-5 (IL-5) . The βc subunit is expressed at lower levels than GMRα on the surface of leukocytes .
Upon binding of GM-CSF to its receptor, the Janus-kinase-2 (JAK-2) is recruited to the cytoplasmic domain of the β subunit, leading to the activation of JAK-2 and subsequent phosphorylation of STAT-5 . This signaling pathway induces the migration of STAT-5 dimers to the nucleus, promoting the transcription of various genes involved in cell differentiation . The GM-CSF receptor is primarily found in myeloid cells and some non-hematopoietic cells, but it is not expressed by lymphoid cells such as T cells .
Recombinant human GM-CSF receptor beta (βc) is produced using recombinant DNA technology, which involves inserting the gene encoding the β subunit into a suitable expression system, such as bacteria or mammalian cells . The recombinant protein is then purified and used for various research and therapeutic applications .
Recombinant human GM-CSF receptor beta is used in research to study the signaling pathways and functions of GM-CSF in various cell types . It is also used in the development of therapeutic strategies targeting GM-CSF signaling in autoimmune diseases and cancer . For example, sargramostim, a recombinant human GM-CSF, has been approved by the US FDA to accelerate bone marrow recovery in patients with bone marrow failure .