# Interleukin 3

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**Interleukin 3** (**IL-3**) is a [protein](/source/Protein) that in [humans](/source/Human) is encoded by the *IL3* [gene](/source/Gene) localized on chromosome 5q31.1.[1][2] Sometimes also called colony-stimulating factor, multi-CSF, mast cell growth factor, MULTI-CSF, MCGF; MGC79398, MGC79399: after removal of the signal peptide sequence, the mature protein contains 133 amino acids in its polypeptide chain. IL-3 is produced as a monomer by activated T cells, monocytes/macrophages and stroma cells.[3] The major function of IL-3 [cytokine](/source/Cytokine) is to regulate the concentrations of various blood-cell types.[4] It induces proliferation and differentiation in both early pluripotent [stem cells](/source/Stem_cell) and committed [progenitors](/source/Progenitor_cell).[5][6] It also has many more specific effects like the regeneration of [platelets](/source/Platelet) and potentially aids in early antibody [isotype switching](/source/Immunoglobulin_class_switching).[7][8]

## Function

Interleukin 3 is an [interleukin](/source/Interleukin), a type of biological signal ([cytokine](/source/Cytokine)) that can improve the body's natural response to disease as part of the [immune system](/source/Immune_system).[8] In conjunction with other β common chain cytokines [GM-CSF](/source/Granulocyte-macrophage_colony-stimulating_factor) and [IL-5](/source/Interleukin_5), IL-3 works to regulate the inflammatory response in order to clear pathogens by changing the abundance of various cell populations via binding at the [interleukin-3 receptor](/source/Interleukin-3_receptor).[7][8]

IL-3 is mainly produced by activated [T cells](/source/T_cell) with the goal of initiating proliferation of various other immune cell types.[6] However, IL-3 has also been shown to be produced in [IgG+](/source/IgG) [B cells](/source/B_cell) and may be involved in earlier antibody [isotype switching.](/source/Immunoglobulin_class_switching)[7] IL-3 is capable of stimulating differentiation of immature [myelomonocytic cells](/source/Myelomonocyte) causing changes to the [macrophage](/source/Macrophage) and [granulocyte](/source/Granulocyte) populations.[6] IL-3 signaling is able to give rise to widest array of cell lineages which is why it has been independently named "multi-CSF" in some older literature.[8]

IL-3 also induces various effector functions in both immature and mature cells that more precisely modulate the body's defense against microbial pathogens.[6][8] IL-3 is also involved in the reconstruction of [platelets](/source/Platelet) via the development of [megakaryocytes](/source/Megakaryocyte).[8]

Interleukin 3 stimulates the differentiation of [multipotent hematopoietic stem cells](/source/Multipotent_hematopoietic_stem_cell) into [myeloid progenitor cells](/source/Myeloid_progenitor_cell) or, with the addition of IL-7, into [lymphoid progenitor cells](/source/Lymphoid_progenitor_cell). In addition, IL-3 stimulates proliferation of all cells in the myeloid lineage ([granulocytes](/source/Granulocyte), [monocytes](/source/Monocyte), and [dendritic cells](/source/Dendritic_cell)), in conjunction with other cytokines, e.g., [Erythropoietin](/source/Erythropoietin) (EPO), [Granulocyte macrophage colony-stimulating factor](/source/Granulocyte_macrophage_colony-stimulating_factor) (GM-CSF), and [IL-6](/source/Interleukin_6).

IL-3 is secreted by basophils and activated [T cells](/source/T_cells) to support growth and differentiation of [T cells](/source/T_cell) from the bone marrow in an immune response. Activated [T cells](/source/T_cells) can either induce their own proliferation and differentiation ([autocrine](/source/Autocrine) signaling), or that of other [T cells](/source/T_cells) ([paracrine](/source/Paracrine) signaling) – both involve [IL-2](/source/Interleukin_2) binding to the [IL-2 receptor](/source/IL-2_receptor) on [T cells](/source/T_cells) (upregulated upon cell activation, under the induction of [macrophage](/source/Macrophage)-secreted [IL-1](/source/Interleukin_1)). The human IL-3 gene encodes a protein 152 amino acids long, and the naturally occurring IL-3 is glycosylated. The human IL-3 gene is located on [chromosome 5](/source/Chromosome_5_(human)), only 9 kilobases from the [GM-CSF](/source/GM-CSF) gene, and its function is quite similar to GM-CSF.

## Receptor

IL-3 is a T cell-derived, pluripotent and hematopoietic factor required for survival and proliferation of hematopoietic progenitor cells. The signal transmission is ensured by high affinity between cell surface [interleukin-3 receptor](/source/Interleukin-3_receptor) and IL-3.[9] This high affinity receptor contains α and β subunits. IL-3 shares the β subunit with IL-5 and granulocyte-macrophage colony-stimulating factor ([GM-CSF](/source/Granulocyte-macrophage_colony-stimulating_factor_receptor)).[10] This β subunit sharing explains the biological functional similarities of different hematopoietic growth factors.[11]

IL-3 receptors can be found on a variety of cell types including many immature [myelomonocytic cells](/source/Myelomonocyte) in the [hemopoietic system](/source/Haematopoiesis) such as hemopoietic progenitor cells, as well as certain myeloid progenitors, [basophils](/source/Basophil), and [eosinophils](/source/Eosinophil).[8]

IL-3/Receptor complex induces [JAK2/STAT5](/source/JAK-STAT_signaling_pathway) cell signalization pathway.[6] It can stimulate transcription factor [c‑myc](/source/Myc) (activation of gene expression) and [Ras pathway](/source/Ras_GTPase) (suppression of apoptosis).[3]

## Discovery

In the early 1960s Ginsberg and Sachs discovered that IL-3 is a potent mast cell growth factor produced from activated [T cells](/source/T_cell).[9] Interleukin 3 was originally discovered in mice and later isolated from humans. The cytokine was originally discovered via the observation that it induced the synthesis of 20alpha-hydroxysteroid dehydrogenase in hematopoietic cells and termed it interleukin-3 (IL-3).[12][13]

## Disease

IL-3 is produced by T cells only after stimulation with [antigens](/source/Antigen) or other specific impulses.

However, it was observed that IL-3 is present in the myelomonocytic leukaemia cell line WEHI-3B. It is thought that this genetic change is the key in development of this leukemia type.[4]

## Immunological therapy

Human IL-3 was first cloned in 1986 and since then clinical trials are ongoing.[14] Post-chemotherapy, IL-3 application reduces chemotherapy delays and promotes regeneration of [granulocytes](/source/Granulocyte) and [platelets](/source/Platelet). However, only IL-3 treatment in bone marrow failure disorders such as [myelodysplastic syndrome](/source/Myelodysplastic_syndrome) (MDS) and [aplastic anemia](/source/Aplastic_anemia) (AA) was disappointing.[11]

It has been shown that combination of IL-3, GM-CSF and stem cell factor enhances peripheral blood stem cells during high-dose chemotherapy.[15][16]

Other studies showed that IL-3 could be a future perspective therapeutic agent in lymphohematopoietic disorders and solid cancers.[17]

## Interactions

Interleukin 3 has been shown to [interact](/source/Protein-protein_interaction) with [IL3RA](/source/IL3RA).[18][19]

## See also

- [Interleukin](/source/Interleukin)

## References

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## Further reading

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- Martinez-Moczygemba M, Huston DP (2003). "Biology of common beta receptor-signaling cytokines: IL-3, IL-5, and GM-CSF". *J. Allergy Clin. Immunol.*. **112** (4): 653–65; quiz 666. [doi:10.1016/j.jaci.2003.08.015](https://doi.org/10.1016/j.jaci.2003.08.015). [PMID 14564341](https://pubmed.ncbi.nlm.nih.gov/14564341)
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- Kitamura T, Sato N, Arai K, Miyajima A (1991). "Expression cloning of the human IL-3 receptor cDNA reveals a shared beta subunit for the human IL-3 and GM-CSF receptors". *Cell*. **66** (6): 1165–1174. [doi:10.1016/0092-8674(91)90039-2](https://doi.org/10.1016/0092-8674(91)90039-2). [PMID 1833064](https://pubmed.ncbi.nlm.nih.gov/1833064). [S2CID 42948973](https://api.semanticscholar.org/CorpusID:42948973)
- Urdal DL, Price V, Sassenfeld HM, Cosman D, Gillis S, Park LS (1989). "Molecular characterization of colony-stimulating factors and their receptors: human interleukin-3". *Ann. N. Y. Acad. Sci.*. **554** (1): 167–176. [Bibcode:1989NYASA.554..167U](https://ui.adsabs.harvard.edu/abs/1989NYASA.554..167U). [doi:10.1111/j.1749-6632.1989.tb22418.x](https://doi.org/10.1111/j.1749-6632.1989.tb22418.x). [PMID 2544122](https://pubmed.ncbi.nlm.nih.gov/2544122). [S2CID 35647863](https://api.semanticscholar.org/CorpusID:35647863)
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- Yang YC, Ciarletta AB, Temple PA, Chung MP, Kovacic S, Witek-Giannotti JS, Leary AC, Kriz R, Donahue RE, Wong GG (1986). "Human IL-3 (multi-CSF): identification by expression cloning of a novel hematopoietic growth factor related to murine IL-3". *Cell*. **47** (1): 3–10. [doi:10.1016/0092-8674(86)90360-0](https://doi.org/10.1016/0092-8674(86)90360-0). [PMID 3489530](https://pubmed.ncbi.nlm.nih.gov/3489530). [S2CID 37207637](https://api.semanticscholar.org/CorpusID:37207637)
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Adapted from the Wikipedia article [Interleukin 3](https://en.wikipedia.org/wiki/Interleukin_3) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Interleukin_3?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.