Overview
Interleukin-3 (IL-3) is a hematopoietic growth factor that promotes the survival, differentiation and proliferation of megakaryocytes, granulocyte-macrophages, erythroid, eosinophils, basophils, and mast cell-committed progenitors. It is mainly secreted by activated T cells, NK cells, mast cells and some stromal cells. It plays a key role in immunomodulation, maintenance of the hematopoietic system and inflammatory response by regulating the proliferation and differentiation of hematopoietic stem cells (HSCs) and progenitor cells. The activity of IL-3 is dependent on co-stimulation with other cytokines.
Signaling pathways
IL-3 activates multiple downstream signaling pathways by binding to the IL-3 receptor (IL-3R), thereby regulating the proliferation, survival, and differentiation of hematopoietic and immune cells.
1. Structure of IL-3 receptor
IL-3R belongs to the type I cytokine receptor family and consists of two subunits:
α subunit (CD123/IL-3Rα): specifically binds IL-3 and determines ligand selectivity.
β subunit (CD131/βc): heterodimers with IL-3Rα responsible for signal transduction (shared with GM-CSF, IL-5 receptors).
2. Receptor activation mechanism
IL-3 binds IL-3Rα → induces conformational change → recruits βc subunit → forms high affinity complex → receptor dimerization → activates JAK2 kinase (binds to βc subunit)
3. Core signaling pathways
Following IL-3R activation, the following signaling cascade reaction are primarily triggered:
(1) JAK-STAT pathway (key proliferation/survival pathway)
JAK2 is recruited and phosphorylated → activates STAT5 (STAT5A/STAT5B)
STAT5 dimerization → nuclear import → regulation of target genes (e.g. Bcl-2, Bcl-xL, c-Myc, Cyclin D1)
Promotes: cell proliferation, anti-apoptosis (up-regulation of Bcl-2 family proteins), hematopoietic stem cell self-renewal
(2) RAS-MAPK pathway (promotes proliferation/differentiation)
IL-3R activation → via Shc-Grb2-SOS complex → activation of RAS → RAF-MEK-ERK cascade reaction
ERK phosphorylates transcription factors (e.g. Elk-1, c-Fos) → promotes cell cycle progression (G1 → S phase).
Function: Synergizes the JAK-STAT pathway to enhance proliferation. Regulates myeloid cell differentiation.
![Figure 1. The IL-3 receptors and the downstream signaling [1]](https://cdn.shopify.com/s/files/1/0803/9419/1166/files/1_41ed5454-918e-43b6-9c29-5b8b18aad6b6_1024x1024.png?v=1756346172)
Figure 1. The IL-3 receptors and the downstream signaling [1]
4. Specific responses in different cell types
|
Cell type |
Main effect |
Key pathways |
|
Hematopoietic stem cells (HSCs) |
Self-renewal, maintenance of multilineage differentiation potential |
JAK-STAT, PI3K-AKT |
|
Myeloid progenitor cells |
Granulocyte/monocyte expansion |
MAPK, STAT5 |
|
Megakaryocytes |
Thrombopoiesis |
JAK2-STAT5, mTOR |
|
Mast cells |
Enhanced survival and degranulation |
PI3K-AKT, NF-κB |
Biological Functions
1. Hematopoiesis Regulation
IL-3 is a multispectral hematopoietic growth factor that mainly acts on early hematopoietic stem cells (HSCs) and progenitor cells to promote their survival, proliferation and differentiation:
(1) Hematopoietic stem cells (HSCs) and progenitor cell support
Maintenance of stem cell self-renewal: inhibits apoptosis (upregulates Bcl-2, Bcl-xL) by activating the JAK-STAT and PI3K-AKT pathways.
Expansion of multipotent progenitor cells: including myeloid-lymphoid progenitor cells (MLP) and granulocyte-macrophage progenitor cells (GMP).
(2) Promotes myeloid cell differentiation
|
Cell type |
Differentiation effects |
Synergistic factors |
|
Granulocytes |
Neutrophil, eosinophil, basophil production |
GM-CSF, G-CSF |
|
Monocytes/Macrophages |
Monocyte differentiation and macrophage polarization |
M-CSF, IL-4 |
|
Dendritic cells (DC) |
Promotes DC precursor cell development (especially plasma cell-like DC) |
FLT3L, GM-CSF |
|
Mast cells |
Progenitor cell differentiation and tissue-resident mast cell survival |
SCF |
|
Megakaryocytes |
Thrombopoiesis (synergistic with TPO) |
TPO, IL-6, IL-11 |
2. Immunomodulation
IL-3 is involved in innate and adaptive immune responses by regulating immune cell function:
(1) Mast cell activation
Promote survival and proliferation: IL-3 is a key growth factor for mast cells.
Enhancement of effector function: triggers histamine, heparin, tryptase release (anaphylaxis). Anti-parasite immunity (e.g., elevated IL-3 levels in worm infections).
(2) Regulation of dendritic cell (DC) function
Up-regulation of MHC-II and co-stimulatory molecules (e.g. CD80/CD86) to enhance antigen presentation.
Promotes TLR signaling response (e.g., antiviral interferon secretion) in plasmacytoid DCs (pDC).
(3) Indirect regulation by T cells and B cells
Indirectly affects Th1/Th2 cell balance by activating DCs or macrophages.
May promote B cell antibody secretion (e.g. IgE production) in chronic inflammation.
3. Inflammation & Pathology
(1) Pro-inflammatory effects
Activate macrophages to secrete pro-inflammatory factors such as TNF-α and IL-6. In allergic diseases (e.g. asthma), IL-3 amplifies the inflammatory response together with mast cells and basophils.
(2) Tumor-related effects
Tumor-promoting: CD123 (IL-3Rα) is highly expressed in acute myeloid leukemia (AML), B-cell malignancies and supports tumor cell survival.
May drive oncogene (e.g. c-Myc) expression through STAT5 sustained activation.
Anti-tumor: enhances tumor antigen presentation by DC vaccines. May improve T-cell expansion when combined with CAR-T therapy (but need to be cautious to avoid exhaustion).
Application of recombinant human IL-3 in cell and gene therapy
1. In vitro hematopoietic stem cell expansion and gene modification
HSCs in vitro culture: IL-3 is often used in combination with other cytokines (e.g., SCF, TPO, FLT3L) to expand umbilical cord blood- or bone marrow-derived HSCs to address the problem of insufficient cell numbers in transplantation.
Gene therapy support: IL-3 improves cell survival and transduction efficiency in hematopoietic stem cell cultures with CAR-T, CAR-NK, or gene editing (e.g., CRISPR).
Figure 2. Hematopoietic stem cells (HSCs) differentiate into different types of cells in response to cytokines
2. Induced pluripotent stem cell (iPSC) differentiation into hematopoietic lineage
In iPSC directed differentiation protocols, IL-3 is combined with factors such as BMP4 and VEGF to promote the formation of hematopoietic progenitor cells (HPCs) for disease modeling or regenerative medicine.
3. Dendritic cell (DC) vaccine preparation
IL-3 enhances the survival and antigen presentation of monocyte-derived DC (moDC), optimizes
the effect of DC vaccines in tumor immunotherapy.
4. Megakaryocyte and Thrombopoiesis
Combined with TPO and IL-6, IL-3 can promote the differentiation of megakaryocytes, which can be used in the treatment of thrombocytopenia or in vitro platelet production.
Yeasen's GMP grade recombinant human IL-3 protein
In order to meet the needs of different stages of cell therapy drug development, Yeasen has developed both research grade and GMP grade recombinant human IL-3. Our research grade and GMP grade proteins have the same manufacturing process and are produced in the same facility with the same performance, which facilitates a seamless transition from preclinical research to clinical production. We performed comprehensive quality control testing of GMP grade IL-3 to ensure strict standards of purity, activity, safety, and consistency. Yeasen's GMP-grade recombinant human IL-3 protein, expressed in E. coli, is highly active, highly pure, and free of animal-derived contamination.
Product Advantages
High purity: >95%, avoiding immune reactions caused by host cell protein (HCP) or DNA residues.
Ultra-low endotoxin: <10 EU/mg, reducing the risk of fever or inflammation.
Batch-to-batch consistency: ensures stability and reproducibility of cell culture.
Compliance: meets regulatory requirements for cell therapy products and supports IND filing.
No animal origin: no animal viruses, no pathogenic substances, no exogenous factor contamination, high safety.
Compliance with regulatory guidelines
The production and quality control of GMP grade proteins comply with the following systems and processes:
1. Comply with the "Pharmacopoeia of the People's Republic of China" 2020 edition of the three general rules: quality control of raw materials and excipients for the production of biological products.
2. Comply with USP Chapter <92> Growth Factors and Cytokines Used in Cell Therapy Manufacturing.
3. Comply with Ph. Eur. General Chapter 5.2.12, Raw Materials of Biological Origin for the Production of Cell-based and Gene Therapy Medicinal Products.
Quality Management System
1. GMP proteins are manufactured, tested and released under a quality management system certified to ISO 13485:2016 to ensure batch-to-batch consistency and material traceability.
2. With Certificate of Analysis (COA).
3. No animal-derived materials and production environment.
4. Production base for raw and auxiliary materials for pharmaceutical products.
5. Support online/offline auditing.
Product safety quality inspection system
Endotoxin: <10 EU/mg
Host DNA residue: < 20 ng/mg
Host protein residue: < 0.5 ng/μg
Sterility test: negative
Mycoplasma: negative
Exogenous virus: negative
Product performance
1. High purity
Figure 3. GMP-grade Human IL-3 protein on SDS-PAGE: the purity is greater than 95%, no heterogeneous proteins.
2. High biological activity
Figure 4. The results of cell proliferation stimulation assay of Human TF-1 cells showed that GMP grade Human IL-3 has a specific activity of >1.7 x 10^6 IU/mg.
3. High Stability
Figure 5. cell proliferation assay of Human TF-1 cells shows that GMP grade Human IL-3 protein is stable at 37℃ for 48 hours after reconstitution.
4. High batch-to-batch consistency
Figure 6. GMP Human IL-3 cell activity of different batches remains consistent with high batch-to-batch consistency.
Figure 7. Cell activity assay results show that GMP Human IL-3 protein is stable after repeated freezing and thawing for 3 times.
Ordering Information
|
Product Name |
Item No. |
Specification |
|
10μg/50μg/1mg |
||
|
Recombinant Human IL-3 Protein |
10μg/50μg/100μg |
|
|
Recombinant Human FGF basic/FGF2/bFGF GMP Protein |
||
|
Recombinant Human IL-6 GMP Protein |
10μg/50μg/1mg |
|
|
Recombinant Human IL-1β GMP Protein |
10μg/50μg/1mg |
Related Literature
[1]. Malgorzata J. P , Robert G , Christian P, et al. IL-3: key orchestrator of inflammation. Front. Immunol., 13 June 2024.