IL 13 Rhesus Macaque

What is IL-13 and how does it compare between rhesus macaques and humans?

Interleukin-13 (IL-13) is a cytokine expressed by the IL13 gene and secreted by multiple cell types, with type 2 helper T-cells (Th2) being the predominant source. In rhesus macaques, mature IL-13 shares 95% amino acid sequence identity with human IL-13, making it an excellent translational model for human immunological research . By comparison, rhesus IL-13 shares only 59% and 60% sequence identity with mouse and rat IL-13, respectively . This high homology between human and rhesus macaque IL-13 explains why rhesus macaques are preferred over rodent models for studying IL-13-mediated immune responses relevant to human diseases.

What is the molecular structure and physical properties of rhesus macaque IL-13?

Rhesus macaque IL-13 is a monomeric protein with a molecular weight of approximately 12.6 kDa, consisting of 114 amino acids . The high solution form features two internal disulfide bonds that contribute to its bundled four α-helix configuration, which is critical for its receptor binding and biological activity . For research applications, recombinant rhesus IL-13 is typically available as a sterile filtered white lyophilized powder that should be stored desiccated at -20°C to maintain stability .

What are the primary immunological functions of IL-13 in rhesus macaques?

IL-13 in rhesus macaques performs several crucial immunoregulatory functions:

• Anti-inflammatory effects: IL-13 exerts potent anti-inflammatory actions on monocytes and macrophages .

• Cytokine inhibition: It suppresses the expression of pro-inflammatory cytokines including IL-1β, TNF-α, IL-6, and IL-8 .

• B-cell modulation: IL-13 enhances B-cell proliferation and induces isotype switching, resulting in increased production of IgE antibodies .

• Th2 development: Studies with targeted deletion models suggest IL-13 plays an important role in Th2 cell development .

• Parasite response: IL-13 appears to be significant in the expulsion of gastrointestinal parasites, as demonstrated in comparable knockout studies .

How does IL-13 expression change during immune responses to infection in rhesus macaques?

The expression pattern of IL-13 in rhesus macaques during infection appears to be disease-specific. In pertussis infection studies, unlike pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) which show significant upregulation, IL-13 levels do not exhibit marked changes . This differential expression highlights the specialized role IL-13 may play in different infectious contexts, suggesting it might be more involved in allergic and parasitic responses rather than bacterial infections like pertussis .

How should researchers design experiments to study IL-13 function in rhesus macaque models?

When designing experiments to study IL-13 function in rhesus macaques, researchers should consider:

• Age selection: Different age cohorts may show varying immune responses. Studies indicate age can significantly affect immune parameters in rhesus macaques .

• Sex consideration: Sex differences have been observed in certain immunological responses in rhesus macaques and should be accounted for in experimental design .

• Origin consideration: Chinese-origin and Indian-origin rhesus macaques display differences in disease pathogenesis and immunological responses . Researchers should select consistent populations or account for this variable.

• Control design: Implement appropriate control conditions, as demonstrated in behavioral studies where test and control trials showed significantly different responses .

• Sampling schedule: For cytokine analysis, implement time-course sampling to capture the dynamic changes in IL-13 expression following immune challenge .

What are the key methodological considerations for measuring IL-13 in rhesus macaque samples?

For optimal IL-13 measurement in rhesus macaque samples:

• Sample collection: Collect serum samples for systemic IL-13 levels. For mucosal responses, consider nasopharyngeal washes (NPW) or bronchoalveolar lavage .

• Assay selection: Use rhesus-specific or cross-reactive human IL-13 immunoassays validated for macaque samples.

• Panel design: Measure IL-13 alongside related cytokines (IL-4, IL-10, IFN-γ) to properly contextualize Th1/Th2 balance .

• Timing: Based on infection studies, consider multiple sampling timepoints (days 0, 5, 10, 15, 25, and 35 post-challenge) to properly capture the dynamics of cytokine responses .

How do genetic differences between rhesus macaque populations affect IL-13 biology?

While specific IL-13 variation between populations has not been fully characterized, broader immunological differences between Chinese-origin and Indian-origin rhesus macaques have been documented. These populations show differences in:

• Disease pathogenesis: Differential susceptibility and progression in certain disease models .

• Immune parameters: Variations in blood chemistry and major histocompatibility complex genetics .

• Cytokine responses: Potential differences in cytokine expression profiles, though specific IL-13 comparative data is limited .

Research indicates that rhesus macaques possess exceptionally high levels of single nucleotide polymorphisms (SNPs) - approximately twice as high as those observed in most human populations . This genetic diversity may impact cytokine expression and function, including IL-13, and should be considered when designing experiments and interpreting results from different rhesus macaque populations.

What challenges exist in translating IL-13 research from rhesus macaque models to human applications?

Despite the high homology between rhesus and human IL-13, several translational challenges exist:

• Genetic diversity: The high genetic diversity in rhesus macaques can create issues for broad applicability of study results .

• Population differences: Variations between Chinese-origin and Indian-origin rhesus macaques in disease susceptibility and immune responses complicate translation .

• Developmental differences: Age-related effects on immune responses may differ between macaques and humans .

• Sex-specific effects: Sex differences in immune responses may not directly parallel those in humans .

How does IL-13 interact with other cytokines in the rhesus macaque immune network?

In rhesus macaque models of infection and inflammation, IL-13 functions within a complex cytokine network. Studies examining pertussis infection have analyzed IL-13 alongside multiple other cytokines including IL-1β, IL-4, IL-6, IL-8, IL-10, IL-12/23p40, IL-17A, IFN-γ, and TNF-α . While IL-13 itself didn't show significant changes during pertussis infection, the upregulation of IL-6, IL-1β, TNF-α, IL-12/23p40, and IL-10 suggests a complex interplay between different immune pathways . This indicates that IL-13 should be studied not in isolation but as part of the broader immune signaling network specific to different disease contexts.

What are the current technical limitations in rhesus macaque IL-13 research?

Current technical limitations include:

• Reagent availability: Limited availability of rhesus-specific research reagents compared to human or mouse models.

• Standardization challenges: Variability in recombinant IL-13 preparations and detection methods across studies.

• Genetic background effects: The high genetic diversity of rhesus macaques (with SNP levels twice that of humans) complicates interpretation of results and requires larger sample sizes .

• Population-specific reference ranges: Incomplete characterization of normal IL-13 expression levels across different rhesus macaque populations.

What are emerging areas of IL-13 research in rhesus macaque models?

Promising future research directions include:

• Population-specific cytokine profiling: Comprehensive characterization of IL-13 expression and function across different rhesus macaque populations.

• Systems biology approaches: Integration of IL-13 data with genomic, transcriptomic, and proteomic datasets to understand broader immune networks.

• Therapeutic targeting studies: Evaluation of IL-13-targeted therapies for allergic and inflammatory conditions using rhesus macaque models.

• Comparative immunology: Detailed comparative analyses of IL-13 signaling pathways between human and rhesus macaque systems.

How can researchers address the variability in IL-13 responses between different rhesus macaque populations?

To address population variability:

• Genetic screening: Implement genetic screening protocols to characterize IL-13 pathway polymorphisms in study subjects.

• Population-specific controls: Establish population-specific reference ranges for normal IL-13 expression.

• Mixed-model statistical approaches: Use statistical methods that account for population differences when analyzing data from diverse rhesus macaque sources.

• Cross-population validation: Validate findings across multiple populations before extrapolating to human applications.