Recombinant Human Interleukin-9 protein (IL9) (Active)
Description
Key Immune Functions
-
Allergic Inflammation: Enhances mast cell/eosinophil recruitment and IgE production .
-
T-Cell Regulation: Drives Th9, Th17, and Treg cell differentiation .
-
Parasite Defense: Promotes gastrointestinal parasite clearance via mucosal immunity .
-
Dual Role in Immunity: Activates pro-inflammatory pathways while suppressing immune responses through Treg and mast cells .
Bioactivity Metrics
| Assay | ED50 | Specific Activity | Source |
|---|---|---|---|
| MO7e cell proliferation | 0.1–1.0 ng/mL | 2.0 × 10⁶ IU/mg | |
| STAT signaling activation | Not quantified | JAK1/JAK3-dependent |
Disease Models
-
Asthma/Allergy: IL-9 induces goblet cell hyperplasia in airway epithelia and mediates anaphylactic responses to ingested allergens .
-
Autoimmunity: Promotes Treg-mediated suppression in colitis and lupus models .
-
Cancer: Linked to pediatric T-cell leukemia progression via Ref-1/APE1 pathways and Hodgkin lymphoma cell survival .
Notable Studies
-
Leukemia: IL-9 overexpression in T-cell leukemia correlates with chemoresistance (Ding et al., 2017) .
-
Contact Dermatitis: IL-9 regulates allergen-specific Th1 responses, exacerbating skin inflammation (Liu et al., 2014) .
-
Mucosal Immunity: Critical for helminth expulsion but dispensable for systemic anaphylaxis (Nowak et al., 2009) .
Product Specs
Generally, the shelf life of the liquid form is 6 months at -20°C/-80°C. The shelf life of the lyophilized form is 12 months at -20°C/-80°C.
Target Background
- This study demonstrates that heightened IL-9 production is associated with the immunopathogenesis of active ulcerative colitis. PMID: 29927662
- IL9 CNS-25/IL9 CNS-18 is a critical and conserved regulatory element for IL-9 production in both mice and humans. PMID: 30442929
- CXCL10, but not CXCL9 or CXCL11, induced IL-9 expression in the liver tissue. PMID: 29860220
- Our study indicates that cartilage degeneration and destruction may be linked to IL-9 production in patients with osteonecrosis of the femoral head. In a human primary chondrocytes culture model, IL-9 increased cartilage degeneration; blocking JAK-STAT signaling mitigated this effect. PMID: 29775946
- Possessing one or more copies of the 1635A allele was associated with increased cytomegalovirus acquisition in HIV-infected infants (42 vs. 11%, P = 0.03) and an elevated risk of Epstein-Barr virus acquisition in HIV-exposed uninfected infants (hazard ratio = 4.2, P = 0.02) compared to 1635GG. PMID: 29112074
- T Helper 9 cells might be the primary source of interleukin-9 (IL-9) in children with allergic asthma. In these patients, IL-9 impairs interferon gamma production and synergistically enhances interleukin-4-induced IgE secretion. PMID: 28724400
- Elevated expression of nuclear factor of activated T cells 1 drives IL-9-mediated allergic asthma. PMID: 26993036
- These findings demonstrate that IL-9-expressing Th9 cells were upregulated in breast cancer patients and potentially possess antitumor roles by enhancing CD8+ T cell-mediated cytotoxicity. PMID: 28918288
- Serum IL-9 and IL-22 are associated with eosinophilia in cow's milk allergy, and a decrease in these two cytokines occurs with cow's milk elimination. PMID: 28934137
- The systemic IL9 level is higher in ulcerative colitis and corresponds with endoscopic inflammation, suggesting its potential application as a negative marker of mucosal healing. PMID: 28652656
- These findings suggest that IL-9 is involved in the pathogenesis of VKH disease, and that IL-9 might also amplify the inflammatory response by increasing the secretion of IL-17, an established proinflammatory cytokine in VKH disease. PMID: 28761327
- Data suggest that the conditions defined for robust induction of interleukin-9 (IL-9) might be pertinent for the development of Vdelta2 T-cell-based immunotherapy. IL-9 might be relevant for the development of Vdelta2 T-cell-based immunotherapy. PMID: 27791087
- An aberrant expression profile of Th9/IL-9 was associated with the pathogenesis of immune thrombocytopenia, potentially through cooperative interaction with Th17/IL-17. PMID: 27662073
- In vitro data indicate that IL9 is regulated by STAT3/5 and in vivo results highlight the pro-neoplastic effect of IL9 on lymphoma T cells. The results suggest that IL9 and its regulators are promising new targets for therapeutic development in mycosis fungoides. PMID: 26851186
- Recent findings suggest that blockade of IL-9 signaling is effective in treating experimental models of autoimmune and chronic inflammatory diseases such as inflammatory bowel diseases, allergic disorders such as food allergy and asthma. PMID: 26976761
- Findings showed that serum levels of IL-9 were elevated in diffuse large-B-cell lymphoma (DLBCL) patients and positive expression of IL-9 was correlated with adverse prognosis indicators. It directly affected proliferation and apoptosis of DLBCL cells by enhancing the expression of p21CIP1 genes and promoted tumor cells to display resistance to chemotherapeutic drugs. PMID: 27364124
- No differences were found in serum levels of IL-9 between different clinical forms of periportal fibrosis in human Schistosoma mansoni infection in Brazil. PMID: 27506138
- PU.1 and IL-9 may play a role in AD pathogenesis and relate to disease severity and clinical eruption types. PMID: 28229452
- Inflammatory cell expression of IL-9 and IL-17C were increased in chronic rhinosinusitis, particularly with allergy and asthma. These interleukins may contribute to the pathogenesis of chronic rhinosinusitis with nasal polyps as well as atopy and may serve as therapeutic targets for disease management. PMID: 26989880
- Serum levels were determined for both T cell polarizing (IL- 33 and IL-12) and T cell effector (IFN-gamma, IL-4, IL-10, IL-17 and IL-9) cytokines in T1DM (type-1 Diabetes Mellitus) subjects with and without microvascular complications (MVC). All the tested cytokines were significantly elevated in T1DM subjects except for IFN-gamma with no significant difference between those with and without MVC. PMID: 27442004
- Results suggest that Th9 cells and IL-9 could play a significant role in the pathogenesis of systemic sclerosis by modulating adaptive and innate immune responses and the production of autoantibodies, indicating the IL-9 pathway as a potential therapeutic target. PMID: 28681919
- TL1A differentially induces expression of TH17 effector cytokines IL-17, -9, and -22 and provides a potential target for therapeutic intervention in TH17-driven chronic inflammatory diseases. PMID: 27733581
- These data indicate that IL-9 is an essential regulator of megakaryopoiesis and a promising therapeutic agent for the treatment of thrombocytopenia such as CIT. PMID: 28450306
- Expression of IL-9 remarkably increases in peripheral blood and liver tissues in patients with primary biliary cirrhosis. PMID: 27916102
- IL-9 promotes proliferation and metastasis in pancreatic cancer cells; this effect may partly involve regulation of the miR-200a/b-catenin axis. PMID: 28349057
- In PsA patients, gammadelta T cell activation is predominantly driven by IL-9/IL-9R interaction, and not solely by IL-23/IL-23R. Collectively, these findings indicate gammadelta T cells and IL-9 as novel players in the pathogenesis of PsA. PMID: 27543964
- Th9 cells produce IL9 that may participate in the pathogenesis of Takayasu's arteritis. PMID: 27629397
- IL-9 serum levels are elevated in patients with systemic lupus erythematosus, rheumatoid arthritis, and systemic sclerosis, but their clinical significance is unknown. [review] PMID: 26921642
- Th9 cell numbers and IL-9 levels are correlated with OA patient symptoms and joint functionality. PMID: 26926842
- IL-9 is functionally active and is a pro-growth/survival factor for the localized pathologic T cells in the synovium of inflammatory arthritis. PMID: 26751012
- Asthmatic children showed an increase in plasma Il9 levels post Mycoplasma pneumoniae infection. PMID: 26191227
- Interleukin-9 Is Associated with Elevated Anti-Double-Stranded DNA Antibodies in Lupus-Prone Mice. PMID: 25902303
- Data demonstrated increased serum levels of IL-9 in systemic lupus erythematosus and rheumatoid arthritis patients, but no association with clinical and laboratory parameters was found. PMID: 26078482
- Identified as a gene target that might interact with environmental exposure to dust mite allergen to increase asthma severity in children. PMID: 25913104
- The association between IL-9 and diabetic kidney disease was complex as it was reduced in diabetes mellitus, but it was at normal levels in those with diabetic kidney disease. PMID: 25542095
- Secretion increased in respiratory epithelial adenomatoid hamartoma tissue. PMID: 26131817
- The results provide evidence that IL-9 is predominantly involved in the pathogenesis of ulcerative colitis, suggesting that targeting IL-9 might become a therapeutic option for patients with UC. PMID: 24957265
- Serum IL-9 is closely related to several clinical features, such as age, B symptoms, and local lymph node involvement. It can also be an independent prognostic factor for extranodal NK/T-cell lymphoma, suggesting a role for IL-9 in disease pathogenesis. PMID: 24722378
- Upregulation of IL-9 induced by pSTAT6 may be involved in the pathogenesis of chronic lymphocytic leukemia. PMID: 24966942
- IL-9 is a key component of memory TH cell peanut-specific responses from children with peanut allergy (PA) and may be a useful biomarker to distinguish between children with PA and those with peanut sensitization. PMID: 25112699
- Overexpression of IL-9 may contribute to the pathogenesis of chronic lymphocytic leukemia and is associated with some adverse prognostic parameters. PMID: 24551294
- This study demonstrates that IL-9, through its direct effects on Th1 and ability to promote IL-4 secretion, has a regulatory role for Th1 lymphocytes in allergic contact dermatitis. PMID: 24487305
- A role for the IL-9/IL-9R axis in the atherosclerotic process is reported. PMID: 24023645
- IL-9 production by memory T-helper (TH)9 cells is higher in the peripheral blood of patients with asthma than in healthy donors. PMID: 24468256
- Recruitment of interleukin 9-producing CD4+ T cells into malignant pleural effusion could be induced by pleural CCL20, and the majority of Th9 cells in MPE displayed the phenotype of effector memory cells. PMID: 23700286
- The activator protein 1 (AP1) family transcription factor BATF (B cell, activating transcription factor-like) was among the genes enriched in Th9 cells and was required for the expression of IL-9 and other Th9-associated genes. PMID: 24216482
- The expansion of the Th9 cell subset, up-regulation of the PU.1 transcription factor, and increased secretion of the IL-9 cytokine may contribute to the pathogenesis of AD. PMID: 24032555
- Higher numbers of TH9 cells occur in normal human skin & blood vs. metastatic lesions of progressive stage IV melanoma. These results suggest a role for IL-9 in tumor immunity. PMID: 22772464
- Children with atopic dermatitis may have higher serum IL-9 levels than healthy children, and IL-9 levels are significantly related to symptom severity. PMID: 22612419
- Substantial renal IL-9 release was observed from deceased donor kidneys. PMID: 22971662
Q&A
What is IL-9 and how was it discovered?
Interleukin-9 (IL-9) was first identified and characterized in the late 1980s as a T-cell and mast cell growth factor. It was initially termed P40 (based on molecular weight) or Mast cell growth-enhancing activity (MEA). The complete amino acid sequencing revealed it as structurally distinct from other T cell growth factors, leading to its designation as IL-9. Human IL-9 was originally identified and cloned based on its stimulatory effect on proliferation of the human myeloid cell line, M07e .
What is the molecular structure of human IL-9?
Human IL-9 is a 14 kDa peptide encoded by a 144 amino acid protein (including leader sequence). The human IL9 gene is located on chromosome 5, in a region syntenic to the mouse Il9 gene on chromosome 13. The IL9 gene is positioned 3.2 Mb telomeric from the IL5/IL13/IL4 loci .
What are the primary biological functions of IL-9?
IL-9 demonstrates pleiotropic functions in the immune system. It mediates allergic inflammation in various tissues, provides a protective role in immunity to certain intestinal parasites, enhances germinal center formation, promotes the generation of class-switched high-affinity antibodies, and stimulates mast cell expansion during allergic inflammation .
What are the optimal storage and handling conditions for recombinant IL-9?
For optimal activity, recombinant human IL-9 should be stored at -80°C and reconstituted in sterile, pH-neutral buffer solutions. Repeated freeze-thaw cycles should be avoided as they can lead to protein degradation. For experiments, IL-9 is typically used at concentrations ranging from 1-50 ng/mL, with 10 ng/mL being commonly used for in vitro assays as demonstrated in protein tyrosine kinase studies with M07e cells .
How can researchers validate the biological activity of recombinant IL-9?
The biological activity of recombinant IL-9 can be validated through several assays:
-
Proliferation assay using IL-9-responsive cell lines such as M07e
-
Phosphorylation analysis using anti-phosphotyrosine antibodies to detect IL-9-induced tyrosine phosphorylation (bands at 105, 97, 85, and 81 kDa)
-
Functional neutralization using anti-IL-9 antibodies
-
Verification of downstream signaling effects using tyrosine kinase inhibitors like genistein
What are the recommended methodologies for studying IL-9 signaling pathways?
For investigating IL-9 signaling pathways, researchers should consider:
-
Immunoblotting with anti-phosphotyrosine monoclonal antibodies to detect activated signaling molecules
-
Comparative analysis with other cytokines (e.g., Steel factor) and stimulants (e.g., TPA)
-
Using specific inhibitors like genistein to block tyrosine kinase activity
-
Examining the activation status of MAP kinase or Raf-1 to distinguish IL-9 signaling from other pathways
How does IL-9 influence T follicular helper (Tfh) cell function?
IL-9 plays a critical role in activating Tfh cells, which are essential for germinal center formation and antibody production. Mice lacking IL-9-specific receptors in Tfh cells (CD4Cre/+Il9rafl/fl) display diminished levels of antigen-specific antibodies alongside reduced germinal center B cells and plasma cells. IL-9 receptor signaling in Tfh cells promotes expression of signature molecules including B-cell lymphoma 6, C-X-C chemokine receptor 5, IL-4, and IL-21. Group 2 innate lymphoid cells (ILC2s) appear to be primary producers of IL-9 under immunizing conditions, potentially induced by leukotrienes released by activated IgD+ B cells around the T-B border .
What is the relationship between IL-9 and mast cell development?
IL-9 significantly promotes mast cell expansion during allergic inflammation through multiple mechanisms:
-
IL-9 receptor (IL-9R) is highly expressed on both mast cell progenitors (MCp) and mature mast cells (mMC), with greatest expression on mMC
-
IL-9 enhances MCp proliferative capacity in vivo, as demonstrated by reduced MCp and mMC proliferation in IL-9 deficient (Il9-/-) mice
-
IL-9 upregulates CCR2 expression on mast cells, facilitating their migration from bone marrow to inflamed tissues like the allergic lung
-
IL-9 stimulation of bone marrow-derived mast cells directly enhances CCR2 expression, while IL-9 neutralization decreases it
How can researchers effectively study the impact of IL-9 in allergic inflammation models?
To effectively study IL-9 in allergic inflammation:
-
Use chronic house dust mite (HDM) challenge models in wild-type and IL-9 deficient (Il9-/-) mice
-
Track mast cell progenitor and mature mast cell proliferation using Ki67 expression markers
-
Employ conditional knockout mice (e.g., CD4Cre/+Il9rafl/fl) to study cell-specific effects
-
Measure allergen-specific IgE and IgG levels in serum to assess humoral responses
-
Analyze levels of mast cell protease 1 (MCPT1) and IL-6 in bronchoalveolar lavage fluid as indicators of mast cell degranulation
What techniques are available for investigating IL-9-mediated cell migration?
Researchers can study IL-9-mediated cell migration using:
-
CCR2 inhibitor experiments to evaluate IL-9's role in promoting CCR2-dependent migration
-
Combination of intranasal IL-9 treatment with intravenous CCR2 inhibitor administration
-
Tracking of mast cell accumulation in bone marrow versus peripheral tissues (trachea, lungs)
-
Adoptive transfer models using T helper cells (particularly TH9 cells) to analyze IL-9-sufficient versus IL-9-deficient conditions
What are the key epigenetic mechanisms controlling IL-9 expression?
IL-9 expression is regulated through several epigenetic mechanisms:
-
Super-enhancers play a crucial role in IL-9 induction during airway inflammation
-
The Il9 CNS-25 regulatory element specifically controls mast cell and basophil IL-9 production
-
STAT5- and STAT6-dependent pathways influence the epigenetic landscape of TH9 cells
-
A complex transcriptional network governs IL-9 expression in T cells
How does the epigenetic regulation of IL-9 differ between cell types?
The epigenetic regulation of IL-9 varies considerably between different immune cell populations:
-
In T cells, particularly TH9 cells, STAT5 and STAT6 pathways play dominant roles in controlling IL-9 expression
-
In mast cells and basophils, the Il9 CNS-25 regulatory element serves as the primary control mechanism
-
Different transcription factor networks are active in innate versus adaptive immune cells
-
Cell-specific super-enhancers determine the magnitude and duration of IL-9 expression in response to inflammatory stimuli
What is the role of IL-9 in intestinal parasite clearance?
IL-9 plays a significant role in immunity against certain intestinal parasites:
How can researchers design experiments to distinguish IL-9-dependent from IL-9-independent anti-parasitic responses?
To distinguish IL-9-dependent from independent responses:
-
Compare wild-type, IL-9-deficient, and IL-9-transgenic mice in parasite challenge models
-
Analyze the effects of neutralizing IL-9 antibodies on worm burden and inflammatory responses
-
Examine the role of other Th2 cytokines (particularly IL-4) in IL-9-deficient animals
-
Evaluate tissue-specific responses, since IL-9 contributes differently to immune responses in different tissues
-
Assess mastocytosis and goblet cell metaplasia as IL-9-dependent parameters independent of parasite clearance
How does IL-9 contribute to anaphylactic reactions?
IL-9 influences anaphylactic reactions in a tissue-dependent manner:
What methodological approaches are recommended for studying IL-9 in allergic airway inflammation?
For studying IL-9 in allergic airway inflammation, researchers should:
-
Utilize house dust mite (HDM) inhalation models in wild-type and IL-9-modified mice
-
Measure HDM-specific IgE and IgG levels in serum
-
Quantify Tfh cells, germinal center B cells, and plasma cells in mediastinal lymph nodes
-
Assess group 2 innate lymphoid cells (ILC2s) as potential IL-9 producers
-
Track CCR2-dependent mast cell migration from bone marrow to lungs
-
Measure mast cell protease 1 (MCPT1) and IL-6 in bronchoalveolar lavage fluid as readouts of mast cell activation
