IL3

Official Full Name

interleukin 3

Organism

Homo sapiens

GeneID

3562

Background

The protein encoded by this gene is a potent growth promoting cytokine. This cytokine is capable of supporting the proliferation of a broad range of hematopoietic cell types. It is involved in a variety of cell activities such as cell growth, differentiation and apoptosis. This cytokine has been shown to also possess neurotrophic activity, and it may be associated with neurologic disorders. [provided by RefSeq, Jul 2008]

Synonyms

IL-3; MCGF; MULTI-CSF;

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Detailed Information

The IL-3 gene encodes a potent pleiotropic hematopoietic growth factor. This cytokine is primarily produced by activated T lymphocytes, while mast cells, basophils, natural killer cells, and even osteoblasts can also serve as sources. IL-3 belongs to the β common-chain cytokine family, and its receptor complex consists of a specific IL-3 receptor α chain and a β common chain shared with IL-5 and GM-CSF. This receptor architecture underlies IL-3's broad functional spectrum and its cross-reactivity with other cytokine signaling pathways. Upon binding to its receptor, IL-3 predominantly activates the JAK2/STAT5 signaling pathway, while also engaging downstream cascades such as RAS/MAPK and PI3K/AKT. The coordinated activity of these signaling networks regulates target cell survival, proliferation, differentiation, and functional activation, highlighting IL-3's central role in hematopoiesis and immune system regulation.

Biological Significance

The core biological significance of IL-3 lies in its role as a multipotent hematopoietic growth factor. It supports the survival, proliferation, and lineage-specific differentiation of a range of hematopoietic progenitors and was historically referred to as a "multi-colony stimulating factor." Its principal target cells include multipotent stem cells, myeloid progenitors, megakaryocyte progenitors, and burst-forming erythroid units, thereby profoundly influencing the generation of granulocytes, monocytes/macrophages, eosinophils, basophils, mast cells, megakaryocytes, and erythrocytes. Beyond promoting hematopoiesis, IL-3 can strongly activate mature myeloid effector cells-for instance, enhancing antibody-dependent cellular cytotoxicity of eosinophils, stimulating histamine release from basophils, and activating phagocytosis and inflammatory cytokine secretion by monocytes/macrophages-thereby playing a critical role in anti-parasitic immunity and allergic responses.

Figure 1. The IL-3 receptor and its downstream signaling. Figure 1. The IL-3 receptor and its downstream signaling. (Podolska MJ, et al., 2024)

Notably, IL-3 functions extend beyond traditional hematopoietic and immune systems. In the central nervous system, IL-3 can be produced by microglia and specific neurons and, through its receptor, exerts neurotrophic and neuroprotective effects, regulating neuronal survival, synaptic plasticity, and responses to neurodegenerative processes. Additionally, IL-3 contributes to bone metabolic homeostasis by inhibiting osteoclast differentiation via suppression of the NF-κB signaling pathway, suggesting a protective role in maintaining bone balance. Therefore, IL-3 represents a key signaling molecule linking adaptive immunity, innate immunity, hematopoiesis, the nervous system, and skeletal physiology.

Clinical Relevance

IL-3's clinical significance is primarily associated with hematologic diseases and therapeutic applications. Pathologically, aberrant IL-3 expression is closely linked to certain hematologic malignancies. For example, in some leukemias, malignant cells may utilize autocrine or paracrine IL-3 signaling to sustain their proliferation and survival, rendering the IL-3 pathway a potential therapeutic target.

Therapeutically, recombinant human IL-3 has historically been investigated for the treatment of bone marrow suppression and cytopenias induced by chemotherapy, radiotherapy, or bone marrow failure disorders, aiming to stimulate multilineage hematopoietic recovery. However, compared with more lineage-specific growth factors such as GM-CSF or G-CSF, IL-3 shows relatively limited efficacy in leukocyte recovery and may provoke more pronounced inflammatory side effects, limiting its broad clinical adoption. Currently, IL-3's primary clinical value lies in its use as a key additive in ex vivo culture systems to expand hematopoietic stem and progenitor cells, particularly in umbilical cord blood expansion and in directing pluripotent stem cells toward hematopoietic lineages. Additionally, IL-3-based immunotoxin fusion proteins are under investigation for targeted therapy against IL-3 receptor-expressing acute myeloid leukemia.

Future advances in understanding IL-3 biology may enable more precise interventions, such as the development of functionally selective antagonists that block pathological IL-3 signaling without impairing physiological hematopoiesis or exploration of its therapeutic potential in neurodegenerative disorders. Nevertheless, balancing its potent hematopoietic stimulation with potential pro-inflammatory and pro-oncogenic risks remains a critical consideration in IL-3 clinical translation.

References

Broughton SE, Dhagat U, Hercus TR, et al. The GM-CSF/IL-3/IL-5 cytokine receptor family: from ligand recognition to initiation of signaling. Immunol Rev. 2012;250(1):277-302.
Dütting S, Gaits-Iacovoni F, Stegner D, et al. A Cdc42/RhoA regulatory circuit downstream of glycoprotein Ib guides transendothelial platelet biogenesis. Nat Commun. 2017;8:15838.
Podolska MJ, Grützmann R, Pilarsky C, et al. IL-3: key orchestrator of inflammation. Front Immunol. 2024 Jun 13;15:1411047.

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