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]
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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.
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]
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]
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]
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]
Interleukin 3 has been shown to interact with IL3RA.[20][21]
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- Overview of all the structural information available in the PDB for UniProt: P08700 (Interleukin-3) at the PDBe-KB.
