Common β Chain Receptor Family Ligands
About Common beta Chain Receptor Family Ligands
The common β-chain receptor family consists of several cytokines, including interleukin 3 (IL-3), interleukin 5 (IL-5), and granulocyte-macrophage colony-stimulating factor (GM-CSF), which are composed of cytokine-specific α-chains and common β-chains. GM-CSF is produced by many different cell types, including activated T cells, B cells, macrophages, mast cells, endothelial cells, and fibroblasts, primarily in response to cytokines or immune and inflammatory stimuli.IL-3, also known as Mast Cell Growth Factor, is a pleiotropic factor produced primarily by activated T cells. IL-3 stimulates the proliferation and differentiation of pluripotent hematopoietic stem cells as well as various lineage-directed progenitors.IL-5 is a T cell-derived factor that promotes the proliferation, differentiation, and activation of eosinophils. In mice, IL-5 is also a growth and differentiation factor for B cells.
The common β chain on GM-CSF, IL-3, and IL-5 receptors interacts with all three ligands to promote some degree of overlap between their regulation of hematopoietic cell signaling involved in hematopoietic stem cell (HSC) proliferation, differentiation, and survival.
Research Progress of Common β Chain Receptor Family Ligands
Common β chain receptor (βcR) family ligands act on hematopoietic stem cells (HSCs) by binding to specific receptors and activating downstream signaling pathways. Upon ligand binding, the receptor undergoes a conformational change that results in activation of Janus kinase (JAK), followed by phosphorylation of STAT (a signal transducer and activator of transcription). Activated STAT then translocates to the nucleus where it regulates the expression of target genes associated with cell proliferation and survival.
Extensive research has been conducted to understand the role of βcR family ligands in hematopoiesis and their potential application in regenerative medicine. It has been shown that these ligands can stimulate HSC expansionin vitro andin vivo, making them valuable tools for stem cell transplantation and gene therapy. For example, IL-3 has been used in ex vivo expansion protocols to increase the number of HSCs transplanted in patients with blood disorders.
In addition, the potential of βcR family ligands to enhance HSC implantation and survival in the transplantation setting has been investigated. Preclinical studies have shown that treatment with IL-3, IL-5, or GM-CSF can enhance hematopoietic reconstitution by increasing the homing and repopulating capacity of transplanted HSC. The immunomodulatory properties of these ligands have also been explored, as they modulate the production and function of immune cells (e.g., eosinophils, basophils, and mast cells).
In conclusion, the common β-chain receptor family of ligands plays a key role in hematopoiesis and has great potential as a hematopoietic stem cell growth factor. Their ability to promote the proliferation and survival of HSCs makes them valuable tools for stem cell research and regenerative medicine applications. Further studies are needed to fully elucidate their mechanisms of action and explore their therapeutic potential in various hematologic diseases.
Reference:
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- Mechanism of activation of the GM-CSF, IL-3, and IL-5 family of receptors[J]. Stem Cells, 2010, 16(5).
- Hercus T, Kan W L, Broughton S E, et al. Role of the beta Common (beta c) Family of Cytokines in Health and Disease[J].Cold Spring Harbor Perspectives in Biology, 2018, 10.
- Martinez-Moczygemba M, Huston DP. Biology of common beta receptor-signaling cytokines: IL-3, IL-5, and GM-CSF[J]. Journal of Allergy & Clinical Immunology. 2003, 112(4):653-665.
- Gregory J. Goodall, Christopher J. Badley, et al.A Model for the Interaction of the GM-CSF, IL-3 and IL-5 Receptors with their ligands[J]. Growth Factors. 1993, 8: 87-97.
