IL-4

Background

Interleukin-4 (IL-4) is an important cytokine in regulating immune responses. It is a glycoprotein composed of four alpha helices and is primarily generated by activated mast cells, T cells, basophils, and eosinophils. IL-4 exerts diverse biological functions, including promoting the differentiation of naive T cells into Th2 cells, decreasing the production of Th1 cells, enhancing B cell proliferation, and antibody class switching to IgE. Additionally, IL-4 inhibits the production of pro-inflammatory cytokines such as IFN-γ and TNF-α, contributing to immune homeostasis and allergic responses. IL-4 can also modulate macrophage activation towards an M2 anti-inflammatory phenotype while inhibiting the classical activation of macrophages to M1 cells, thereby reducing pathological inflammation and promoting wound repair.

Its Gene ID: 3565, UniProtKB ID: P05112, and OMIM ID: 147780.

IL-4 Receptor System and Signaling Pathways

IL-4 initiates signal transduction through the IL-4Rα. There are two types of receptor complexes:

• Type 1 receptor, composed of IL-4Rα and gamma chain (γc) dimerization, which is expressed on various immune cells and binds IL-4 with high affinity, initiating Th2 differentiation and IgE production;
• Type 2 receptor, composed of IL-4Rα and IL-13Rα1, has broader expression and binds IL-4 and IL-13, regulating inflammatory responses and tissue repair.

Activation of Type 1 receptor triggers JAK/STAT6 pathway: IL-4 binds IL-4Rα, activating JAK kinases (JAK1 and JAK3) that phosphorylate STAT6. Phosphorylated STAT6 dimerizes and translocates to the nucleus, promoting transcription of genes involved in Th2 differentiation and IgE class-switching. Type 2 receptors also signal via JAK family kinases (JAK1 and Tyk2), and most of their information is also transmitted by STAT6, leading to the phosphorylation and nuclear translocation of STAT6 upon ligand binding.

Fig.1 IL-4 receptors and their signaling transduction.^{1, 3}

Role of IL-4 in Diseases

IL-4 plays diverse roles in several immune diseases. In allergic diseases, it promotes IgE production and allergic inflammation. In tumors, IL-4 can modulate the tumor microenvironment and support tumor-associated macrophages, influencing immune responses and enhancing tumor progression. IL-4 may contribute to neuroinflammation and neuroprotection in the nervous system, depending on context. IL-4 is also involved in some autoimmune diseases, infection, and development of HIV/AIDS, etc. Understanding IL-4's involvement in these contexts is critical for designing targeted treatments and interventions to regulate modulating immune responses and disease progression.

Antibodies Targeting IL-4

Antibodies targeting IL-4 are crucial in detecting IL-4 levels in biological samples, particularly in ELISA experiments. These antibodies bind specifically to IL-4, allowing for accurate cytokine quantification. This may aid in studies of disease diagnosis and monitoring therapeutic responses aimed at IL-4-mediated pathways. Additionally, blocking antibodies for IL-4 inhibits its interaction with receptors, disrupting downstream signaling pathways involved in allergic reactions and inflammation. Research utilizing IL-4-blocking antibodies has demonstrated efficacy in mitigating symptoms of allergic diseases and asthma in various experimental models by inhibiting IL-4-dependent events. This underscores their potential in diagnostic assays and as therapeutic agents targeting IL-4-mediated immunological disorders.

Creative Biolabs provides compassionate human IL-4 ELISA Kit products that ensure reliable detection and precise analysis to accelerate your scientific research.

IL-4 Functional Service

Creative Biolabs delivers a comprehensive collection of IL-4-related reagents, including specialized ELISA kits for IL-4 detection. These tools excel in revealing and analyzing interactions involving the human IL-4 protein and various other components. Consequently, they are essential resources in research dedicated to formulating therapeutic strategies for disease treatment.

Fig.2 Quantification of cytokine concentrations via ELISA assay.^{2, 3}

The study explored myeloma cells’ capability to act as antigen-presenting cells (APCs), potentially boosting Th2 proliferation when stimulated by microbial antigens. Researchers employed mixed lymphocyte reactions and utilized assays such as the CCK8-kit for cell proliferation, flow cytometry for surface marker analysis, and an ELISA kit for cytokine quantification such as IL-4. Findings revealed that RPMI 8266 cells stimulated Th2 to secrete higher IL-4 levels, enhancing myeloma clonogenicity in a dose-dependent fashion. Blocking with anti-HLADR IgG2b disrupted IL-4 secretion and clonogenicity. This suggests that myeloma cells may support tumor progression by acting as APCs, highlighting a potential target for therapeutic interventions.

Creative Biolabs delivers specialized insights into IL-4 functionality through in-depth investigations of interaction dynamics and rigorous functional assessments. These personalized services are crafted to meet the specific demands of distinguished clients, significantly propelling both clinical and scientific research initiatives forward.

References

1. Shi, Jingwei, et al. "Involvement of IL-4, IL-13 and their receptors in pancreatic cancer." International journal of molecular sciences 22.6 (2021): 2998.
2. Tian, Faqing, et al. "Microbial antigens-loaded myeloma cells enhance Th2 cell proliferation and myeloma clonogenicity via Th2–myeloma cell interaction." BMC cancer 19 (2019): 1-9.
3. Distributed under Open Access license CC BY 4.0, without modification.