Interleukin 3

Interleukin 3 (IL-3) is a protein that in humans is encoded by the IL3 gene localized on chromosome 5q31.1.^[3][4] 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.^[5] The major function of IL-3 cytokine is to regulate the concentrations of various blood-cell types.^[6] It induces proliferation and differentiation in both early pluripotent stem cells and committed progenitors.^[7][8] It also has many more specific effects like the regeneration of platelets and potentially aids in early antibody isotype switching.^[9][10]

IL3
Available structures PDB Human UniProt search: PDBe RCSB List of PDB id codes 1JLI
Identifiers
Aliases	IL3, interleukin 3, IL-3, MCGF, MULTI-CSF
External IDs	OMIM: 147740; HomoloGene: 47938; GeneCards: IL3; OMA:IL3 - orthologs
Gene location (Human) Chr. Chromosome 5 (human)[1] Band 5q31.1 Start 132,060,655 bp[1] End 132,063,204 bp[1]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Achilles tendon bone marrow lymph node appendix n/a More reference expression data BioGPS More reference expression data
Gene ontology Molecular function growth factor activity interleukin-3 receptor binding cytokine activity protein tyrosine kinase activity interleukin-1 receptor binding Cellular component extracellular region intracellular anatomical structure extracellular space Biological process MAPK cascade embryonic hemopoiesis cell-cell signaling nervous system development positive regulation of peptidyl-tyrosine phosphorylation immune response peptidyl-tyrosine phosphorylation positive regulation of tyrosine phosphorylation of STAT protein fever generation regulation of cytokine-mediated signaling pathway regulation of signaling receptor activity cytokine-mediated signaling pathway positive regulation of cell population proliferation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3562 n/a Ensembl ENSG00000164399 n/a UniProt P08700 n/a RefSeq (mRNA) NM_000588 n/a RefSeq (protein) NP_000579 n/a Location (UCSC) Chr 5: 132.06 – 132.06 Mb n/a PubMed search [2] n/a
Wikidata
View/Edit Human

Function

Interleukin 3 is an interleukin, a type of biological signal (cytokine) that can improve the body's natural response to disease as part of the immune system.^[10] In conjunction with other β common chain cytokines GM-CSF and IL-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.^[9][10]

IL-3 is mainly produced by activated T cells with the goal of initiating proliferation of various other immune cell types.^[8] However, IL-3 has also been shown to be produced in IgG+ B cells and may be involved in earlier antibody isotype switching.^[9]  IL-3 is capable of stimulating differentiation of immature myelomonocytic cells causing changes to the macrophage and granulocyte populations.^[8] 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.^[10]

IL-3 also induces various effector functions in both immature and mature cells that more precisely modulate the body's defense against microbial pathogens.^[8][10] IL-3 is also involved in the reconstruction of platelets via the development of megakaryocytes.^[10]

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

IL-3 is secreted by basophils and activated T cells to support growth and differentiation of T cells from the bone marrow in an immune response. Activated T cells can either induce their own proliferation and differentiation (autocrine signaling), or that of other T cells (paracrine signaling) – both involve IL-2 binding to the IL-2 receptor on T cells (upregulated upon cell activation, under the induction of macrophage-secreted IL-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, only 9 kilobases from the 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 and IL-3.^[11] 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).^[12] This β subunit sharing explains the biological functional similarities of different hematopoietic growth factors.^[13]

IL-3 receptors can be found on a variety of cell types including many immature myelomonocytic cells in the hemopoietic system such as hemopoietic progenitor cells, as well as certain myeloid progenitors, basophils, and eosinophils.^[10]

IL-3/Receptor complex induces JAK2/STAT5 cell signalization pathway.^[8] It can stimulate transcription factor c‑myc (activation of gene expression) and Ras pathway (suppression of apoptosis).^[5]

Discovery

In the early 1960s Ginsberg and Sachs discovered that IL-3 is a potent mast cell growth factor produced from activated T cells.^[11] 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).^[14][15]

Disease

IL-3 is produced by T cells only after stimulation with antigens 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.^[6] 

Immunological therapy

Human IL-3 was first cloned in 1986 and since then clinical trials are ongoing.^[16] Post-chemotherapy, IL-3 application reduces chemotherapy delays and promotes regeneration of granulocytes and platelets. However, only IL-3 treatment in bone marrow failure disorders such as myelodysplastic syndrome (MDS) and aplastic anemia (AA) was disappointing.^[13]

It has been shown that combination of IL-3, GM-CSF and stem cell factor enhances peripheral blood stem cells during high-dose chemotherapy.^[17][18]

Other studies showed that IL-3 could be a future perspective therapeutic agent in lymphohematopoietic disorders and solid cancers.^[19]

Interactions

Interleukin 3 has been shown to interact with IL3RA.^[20][21]

See also

• Interleukin