IL17A Canine

What is IL17A and what role does it play in canine immune function?

IL17A (Interleukin-17A) is a pro-inflammatory cytokine belonging to the IL17 family that plays a crucial role in canine immune regulation. It is a 17.5 kDa protein that forms homodimers or heterodimers with IL17F to signal through the receptor complex consisting of IL17RA and IL17RC subunits . In canines, IL17A is primarily produced by Th17 lymphocytes following stimulation by IL-23, though it can also be secreted by gamma δ T cells and CD8+ T cells .

IL17A functions as a key mediator of inflammatory responses by inducing the production of various cytokines (IL-1β, TNFα, G-CSF, IL-6), chemokines (MCP-1/CCL2, CXCL1, CXCL2, CCL20), and antimicrobial proteins . This cytokine has been implicated in both protective immunity against pathogens and pathological inflammatory conditions in dogs, making it a significant area of study for understanding canine immune regulation and disease processes.

How does canine IL17A compare structurally and functionally to human IL17A?

Canine IL17A shares significant structural and functional homology with human IL17A, exhibiting approximately 81% amino acid sequence identity . Both canine and human IL17A contain a structural motif termed a cysteine knot, which characterizes the IL17 family. Unlike most cysteine knot superfamily members that use three intrachain disulfide bonds, IL17 family molecules generate the same structural form with only two disulfide links .

Functionally, both human and canine IL17A act as pro-inflammatory mediators that stimulate the production of cytokines and chemokines from target cells. They both signal through similar receptor complexes composed of IL17RA and IL17RC subunits. The effective dose (ED50) for canine IL17A's biological activity is approximately 0.3-1.5 ng/mL , comparable to human IL17A potency ranges.

This high degree of homology makes comparative studies between species valuable, though researchers should remain aware of species-specific differences when designing cross-species experiments or when considering the translational potential of canine models for human diseases.

What are the current methodologies for detecting IL17A in canine samples?

Several validated methodologies are available for detecting IL17A in canine samples, each with specific applications depending on research objectives:

• Enzyme-Linked Immunosorbent Assay (ELISA): Commercial ELISA kits specific for canine IL17A allow quantification of IL17A in serum, plasma, and cell culture supernatants. This method was successfully used to monitor changes in serum IL17A concentration in dogs with immune-mediated hemolytic anemia .

• Flow Cytometry: Intracellular staining for IL17A can be performed using specific anti-IL17A antibodies. This approach is particularly valuable for identifying IL17A-producing cell populations. Protocols typically involve cell stimulation (e.g., with PMA/Ionomycin in the presence of Golgi inhibitors) followed by fixation, permeabilization, and antibody staining .

• Immunohistochemistry/Immunofluorescence: These techniques allow for the visualization of IL17A-producing cells within tissue sections, providing spatial information about IL17A expression in the context of disease pathology.

• PCR-based Techniques: Quantitative PCR can measure IL17A mRNA expression in various canine tissues and cells, providing insights into transcriptional regulation.

The selection of an appropriate detection method should consider factors such as sensitivity requirements, sample type, and whether protein or mRNA detection is more relevant to the research question.

How should researchers design in vitro experiments to study IL17A effects on canine epithelial cells?

When designing in vitro experiments to study IL17A effects on canine epithelial cells, researchers should consider the following methodological approach:

• Cell Selection and Preparation:

  • Use immortalized canine epithelial cell lines (such as canine buccal epithelial cells) or primary epithelial cells isolated from relevant tissues

  • Verify epithelial cell identity through markers such as CD49f (positive) and cytokeratin 3 (typically negative in buccal epithelial cells)

  • Culture cells in appropriate media with controlled conditions (temperature, CO2, humidity)

• Stimulation Protocol:

  • Use recombinant canine IL17A at physiologically relevant concentrations (starting with 0.3-1.5 ng/mL based on ED50)

  • Include appropriate controls: unstimulated cells, positive controls (known stimulants like TLR ligands), and where relevant, inhibitors or blocking antibodies

  • Determine optimal stimulation timeframe through pilot time-course experiments

• Readout Selection:

  • Measure secretion of inflammatory mediators (CXCL8, IL-6) by ELISA

  • Assess changes in gene expression by qRT-PCR for key inflammatory genes

  • Consider analyzing signaling pathway activation (phosphorylation of STAT3, NF-κB)

• Experimental Variations:

  • Test dose-dependent effects by using a range of IL17A concentrations

  • Investigate synergistic effects with other cytokines (e.g., IFN-γ, TNF-α)

  • Compare effects of IL17A homodimers vs. IL17A/F heterodimers

  • Study the modulatory effects of anti-inflammatory agents (e.g., calcitriol)

A well-designed experiment with canine buccal epithelial cells demonstrated that recombinant canine IL17A significantly increased CXCL8 secretion, while the vitamin D metabolite calcitriol suppressed this response . This experimental design provides valuable insights into epithelial cell responses that may be relevant to inflammatory processes in canine tissues.

What protocol should be followed when using recombinant canine IL17A protein in research applications?

When working with recombinant canine IL17A protein in research applications, the following protocol should be followed to ensure optimal bioactivity and experimental consistency:

• Protein Selection:

  • Choose E. coli-derived recombinant canine IL17A protein spanning amino acids Gly81-Ala210

  • Consider whether carrier-free (CF) or bovine serum albumin (BSA)-containing formulations are more appropriate for your specific application

• Reconstitution Procedure:

  • For BSA-containing formulations: Reconstitute at 100 μg/mL in 4 mM HCl containing at least 0.1% human or bovine serum albumin

  • For carrier-free formulations: Reconstitute at 100 μg/mL in 4 mM HCl

  • Allow complete dissolution by gentle swirling rather than vortexing to avoid protein denaturation

• Storage and Handling:

  • Store reconstituted protein at -20°C or -80°C in single-use aliquots

  • Avoid repeated freeze-thaw cycles that can compromise protein activity

  • Use a manual defrost freezer for long-term storage

  • When thawing for use, maintain protein on ice and use within the same day

• Experimental Usage:

  • Dilute to working concentrations in appropriate buffers immediately before use

  • For cell stimulation assays, start with concentrations based on the established ED50 of 0.3-1.5 ng/mL

  • Include appropriate controls in all experiments, such as heat-inactivated protein or irrelevant recombinant proteins

  • Verify bioactivity through established assays, such as stimulation of CXCL8 secretion from canine epithelial cells

Following these guidelines will help ensure reproducible results when working with recombinant canine IL17A protein and allow meaningful comparisons between different studies.

What are the best practices for measuring IL17A concentrations in canine serum samples?

When measuring IL17A concentrations in canine serum samples, researchers should follow these best practices to ensure reliable and reproducible results:

• Sample Collection and Processing:

  • Collect blood in appropriate tubes (typically serum separator tubes)

  • Allow complete clotting at room temperature (30-60 minutes) before centrifugation

  • Centrifuge at 1,000-2,000g for 10 minutes to separate serum

  • Aliquot serum to avoid repeated freeze-thaw cycles and store at -80°C until analysis

  • Process all samples consistently to minimize pre-analytical variability

• ELISA Selection and Validation:

  • Use a commercially available ELISA kit specifically validated for canine IL17A detection

  • Verify the detection range, sensitivity, and specificity of the assay

  • Include appropriate controls in each assay run (low, medium, and high concentration standards)

  • Validate the assay for your specific sample type if the manufacturer hasn't done so

• Assay Performance:

  • Run all samples in duplicate or triplicate to assess intra-assay variability

  • Include quality control samples across multiple plates to assess inter-assay variability

  • Construct standard curves for each plate and ensure acceptable curve fitting (r² ≥ 0.98)

  • Calculate and report coefficients of variation for intra- and inter-assay measurements

• Data Interpretation:

  • Establish reference ranges for your laboratory and canine population

  • Consider the clinical context when interpreting values (e.g., disease state, treatment status)

  • Be aware that normal canine serum IL17A concentrations are typically around 10.52 pg/mL in healthy dogs, while dogs with conditions like IMHA may have elevated levels (around 19.52 pg/mL)

• Longitudinal Monitoring:

  • When following disease progression or treatment response, collect samples at consistent time points

  • A proven approach is to measure at baseline (day 0), after 48 hours (day 2), and after 96 hours (day 4) as demonstrated in IMHA research

Following these practices will help ensure the generation of reliable data on canine IL17A concentrations that can be meaningfully interpreted in research and potentially clinical contexts.

How can IL17A serve as a biomarker in canine immune-mediated hemolytic anemia (IMHA)?

IL17A shows significant potential as a biomarker in canine immune-mediated hemolytic anemia (IMHA), particularly for monitoring disease progression and predicting outcomes:

• Prognostic Value:
  Research has demonstrated that serum IL17A concentration exhibits different trajectories in surviving versus non-surviving IMHA dogs. While serum IL17A levels at day 0 (admission) may not significantly differ between survivors and non-survivors, the trend during hospitalization becomes highly informative. Surviving dogs show a significant decrease in serum IL17A concentration by day 2 and day 4, whereas non-surviving dogs maintain elevated levels . This difference becomes statistically significant, making IL17A a potential predictor of mortality risk.

• Treatment Response Monitoring:
  The temporal pattern of IL17A concentration can serve as an indicator of response to immunosuppressive therapy. The failure of IL17A levels to decrease during treatment may signal inadequate suppression of the aberrant immune response, potentially indicating the need for adjustment of therapeutic protocols .

• Disease Activity Assessment:
  Although initial studies did not find direct correlations between serum IL17A concentrations and other clinical parameters such as total bilirubin, lactate concentrations, or CBC parameters , the persistent elevation of IL17A likely reflects ongoing immune dysregulation. This provides a unique immunological perspective on disease activity that complements traditional clinical and laboratory assessments.

• Implementation Considerations:
  To effectively implement IL17A as a biomarker in clinical research or practice, samples should be collected at standardized timepoints: at diagnosis (day 0), after 48 hours (day 2), and after 96 hours (day 4) . Serial measurements are essential, as the trajectory of change rather than absolute values appears most informative for prognosis.

These findings suggest that monitoring serum IL17A concentrations during the acute stages of IMHA could provide valuable information for clinical decision-making and prognostication, potentially enabling more tailored therapeutic approaches for individual dogs.

What role does IL17A play in the immunopathogenesis of canine autoimmune diseases?

IL17A plays a complex and multifaceted role in the immunopathogenesis of canine autoimmune diseases, contributing to disease initiation, progression, and tissue damage through several mechanisms:

• Immune Dysregulation:
  In canine autoimmune diseases like immune-mediated hemolytic anemia (IMHA), IL17A represents a key component of immune dysregulation. While physiological IL17A production contributes to host defense, dysregulated production can facilitate autoimmune responses. Research has shown elevated serum IL17A concentrations in dogs with IMHA compared to healthy controls (though this difference did not reach statistical significance in all studies, with mean values of 19.52 pg/mL vs 10.52 pg/mL) . This elevation mirrors findings in human autoimmune hemolytic anemia, suggesting conserved pathogenic mechanisms across species.

• Tissue Inflammation:
  IL17A amplifies inflammatory responses in target tissues by:

  • Stimulating epithelial cells to secrete pro-inflammatory chemokines such as CXCL8, which recruits neutrophils to inflammatory sites

  • Inducing the production of pro-inflammatory cytokines from various cell types

  • Promoting the expression of tissue-damaging enzymes and reactive oxygen species

• Cellular Recruitment and Activation:
  IL17A contributes to the trafficking and activation of inflammatory cells in autoimmune diseases by:

  • Enhancing the expression of adhesion molecules on endothelial cells

  • Inducing the production of chemokines that attract neutrophils, macrophages, and other inflammatory cells

  • Amplifying pro-inflammatory feedback loops through stimulation of multiple cell types

• Interaction with Other Immune Pathways:
  IL17A does not act in isolation but cooperates with other cytokines to drive autoimmunity:

  • IL17A can synergize with cytokines like IFN-γ to induce enhanced inflammatory responses in canine epithelial cells

  • The balance between IL17A and regulatory cytokines like IL-10 and TGF-β1 likely influences disease outcomes

• Therapeutic Implications:
  Understanding IL17A's role in canine autoimmune diseases has therapeutic implications:

  • The observation that IL17A levels decrease in surviving IMHA dogs suggests that successful immunosuppressive therapy may work partly by reducing IL17A production

  • Specific IL17A-targeting approaches, which have proven successful in human autoimmune diseases, might be explored for canine applications

These insights into IL17A's role in canine autoimmune diseases provide a foundation for further investigation into targeted therapeutic approaches and more precise disease monitoring.

How does IL17A interact with epithelial cells in canine inflammatory conditions?

IL17A exhibits significant interactions with epithelial cells in canine inflammatory conditions, serving as a critical mediator between immune cells and epithelial barriers:

• Activation of Pro-inflammatory Pathways:
  Research with immortalized canine buccal epithelial cells has demonstrated that recombinant canine IL17A significantly increases the secretion of CXCL8 (IL-8), a potent neutrophil chemokine . This activation occurs through binding to the IL17RA/RC receptor complex on epithelial cells, triggering downstream signaling cascades that activate transcription factors such as NF-κB and AP-1, which regulate inflammatory gene expression.

• Epithelial Barrier Function Modulation:
  IL17A can influence the integrity of epithelial barriers by:

  • Regulating the expression of tight junction proteins

  • Inducing antimicrobial peptide production, which helps protect against pathogens but may also contribute to tissue damage during excessive inflammation

  • Promoting epithelial cell proliferation and tissue repair mechanisms in some contexts

• Synergistic Effects with Other Mediators:
  IL17A's effects on canine epithelial cells are often enhanced in the presence of other inflammatory mediators:

  • Similar to the effects seen with IL17A, certain allergen extracts (such as Dermatophagoides farinae and Alternaria alternata) and Toll-like receptor ligands (Pam3CSK4, heat-killed Listeria monocytogenes, FSL-1, flagellin) also increase CXCL8 secretion from canine epithelial cells

  • These parallel effects suggest potential synergistic pathways between allergen sensing, microbial recognition, and IL17A-mediated inflammation

• Regulatory Mechanisms:
  The interaction between IL17A and epithelial cells is subject to regulatory influences:

  • The vitamin D metabolite calcitriol significantly suppresses IL17A-induced CXCL8 production in canine epithelial cells

  • This finding suggests potential therapeutic applications for vitamin D in modulating IL17A-driven epithelial inflammation in canine diseases

• Tissue-Specific Responses:
  While much research has focused on canine buccal epithelial cells, IL17A likely interacts with epithelial cells throughout the body, with responses that may vary by tissue type:

  • Skin epithelial cells have shown similar pro-inflammatory responses to IL17A stimulation

  • Respiratory, intestinal, and urogenital epithelial responses to IL17A represent important areas for future investigation in canine disease models

These interactions between IL17A and epithelial cells form a crucial component of inflammatory responses in various canine diseases and offer potential targets for therapeutic intervention.

What are the key considerations when interpreting varying IL17A levels across different canine disease studies?

When interpreting varying IL17A levels across different canine disease studies, researchers should consider several factors that may influence results and their interpretation:

By carefully considering these factors, researchers can more accurately interpret varying IL17A results across studies and identify genuinely significant biological patterns versus methodological artifacts.

How can researchers address the challenges in studying IL17A expression in canine tissues?

Researchers face numerous challenges when studying IL17A expression in canine tissues, requiring strategic approaches to overcome these limitations:

• Tissue Sampling and Preservation Challenges:

  • Solution: Implement standardized tissue collection protocols that minimize time between sampling and preservation

  • Approach: For RNA analysis, use RNAlater or flash freezing in liquid nitrogen immediately after collection

  • Consideration: Create tissue biobanks with well-characterized samples to enable larger studies

• Cell-Specific Expression Analysis:

  • Challenge: IL17A can be produced by multiple cell types (Th17 cells, γδ T cells, CD8+ T cells)

  • Solution: Combine immunohistochemistry with specific cell markers to identify IL17A-producing cells

  • Advanced Approach: Consider single-cell RNA sequencing to comprehensively map IL17A expression patterns in complex tissues

• Low Abundance and Detection Limitations:

  • Challenge: IL17A is often expressed at low levels, making detection difficult

  • Solution: Employ signal amplification methods such as tyramide signal amplification for immunohistochemistry

  • Alternative Approach: Use more sensitive digital PCR techniques rather than conventional qPCR for mRNA detection

• Lack of Validated Reagents:

  • Challenge: Limited availability of canine-specific IL17A antibodies with validated specificity

  • Solution: Rigorously validate antibodies using appropriate positive and negative controls

  • Approach: Use recombinant canine IL17A protein as positive control and employ blocking peptides to confirm specificity

• Functional Validation:

  • Challenge: Detecting IL17A protein doesn't necessarily indicate biological activity

  • Solution: Complement expression studies with functional assays, such as measuring CXCL8 secretion from epithelial cells

  • Approach: Develop reporter cell lines expressing canine IL17 receptors to directly measure biological activity

• Tissue Heterogeneity:

  • Challenge: Bulk tissue analysis may mask important cell-specific expression patterns

  • Solution: Use laser capture microdissection to isolate specific regions of interest

  • Consideration: Combine tissue microarrays with digital pathology for higher throughput analysis of expression patterns

• Longitudinal Assessment:

  • Challenge: Capturing temporal changes in IL17A expression during disease progression

  • Solution: Establish minimally invasive sampling protocols that allow for repeated measurements

  • Approach: When ethical and clinically feasible, obtain sequential biopsies at defined disease timepoints

By implementing these strategic approaches, researchers can generate more reliable and informative data on IL17A expression in canine tissues, advancing our understanding of its role in health and disease.

What are the current limitations in translating IL17A research findings from canine models to human applications?

Despite the significant homology between canine and human IL17A (81% amino acid sequence identity) , several important limitations exist in translating research findings between species:

Understanding these limitations and strategically addressing them can maximize the translational value of canine IL17A research while acknowledging the inherent constraints of cross-species extrapolation.

What emerging technologies will advance our understanding of IL17A function in canine immunology?

Several cutting-edge technologies are poised to significantly advance our understanding of IL17A function in canine immunology:

• Single-Cell Sequencing Technologies:

  • Single-cell RNA sequencing (scRNA-seq) will enable comprehensive mapping of IL17A-producing cell populations in canine tissues with unprecedented resolution

  • Single-cell ATAC-seq can reveal chromatin accessibility patterns governing IL17A expression in different immune cell subsets

  • Spatial transcriptomics will provide insights into the tissue distribution of IL17A-producing cells in their native microenvironment

  • These approaches will help resolve longstanding questions about which specific cell populations produce IL17A in different canine diseases

• CRISPR/Cas9 Gene Editing:

  • Creation of canine cell lines with IL17A or IL17R gene knockouts to study signaling mechanisms

  • Development of reporter cell lines expressing fluorescent proteins under the control of the IL17A promoter to monitor expression dynamics

  • Targeted mutation of specific regulatory elements to understand transcriptional control of IL17A in canine cells

• Organoid and 3D Culture Systems:

  • Canine tissue-specific organoids will provide more physiologically relevant models for studying IL17A effects on epithelial barriers

  • Co-culture systems combining immune cells with tissue organoids will enable analysis of complex cellular interactions

  • These systems will better recapitulate the three-dimensional tissue architecture in which IL17A functions

• Advanced Imaging Techniques:

  • Multiplex immunofluorescence imaging allowing simultaneous detection of IL17A alongside multiple cellular markers

  • Intravital microscopy to visualize IL17A-producing cells and their interactions in living tissues

  • Mass cytometry imaging (IMC) to analyze dozens of proteins simultaneously in tissue sections with subcellular resolution

• Proteomics and Metabolomics:

  • Phosphoproteomics to map IL17A-induced signaling pathways in canine cells with high resolution

  • Secretome analysis to comprehensively characterize factors released by cells in response to IL17A stimulation

  • Metabolomics to identify metabolic changes induced by IL17A signaling in different canine cell types

• Computational and Systems Biology Approaches:

  • Network analysis to understand IL17A within the broader context of immune signaling networks

  • Machine learning algorithms to identify patterns in complex datasets relating IL17A expression to disease phenotypes

  • Multi-omics data integration to develop comprehensive models of IL17A function across biological scales

• Advanced Immunomonitoring:

  • Mass cytometry (CyTOF) for high-dimensional analysis of IL17A-producing cells in canine samples

  • Spectral flow cytometry enabling simultaneous detection of more markers to better characterize IL17A-producing cell subsets

  • Liquid biopsy approaches for less invasive monitoring of circulating IL17A and IL17A-producing cells

These emerging technologies will collectively transform our understanding of IL17A biology in canines, enabling more precise targeting of this pathway for therapeutic applications and providing deeper insights into its role in health and disease.

How might targeting IL17A therapeutically benefit canine autoimmune and inflammatory diseases?

Therapeutic targeting of IL17A holds substantial promise for treating canine autoimmune and inflammatory diseases, with several potential approaches and benefits:

• Therapeutic Modalities:

  • Monoclonal Antibodies: Development of caninized anti-IL17A antibodies similar to human therapeutics like secukinumab and ixekizumab

  • Receptor Antagonists: Small molecules or biologics that block the interaction between IL17A and its receptors (IL17RA/RC)

  • Small Molecule Inhibitors: Compounds targeting the intracellular signaling pathways downstream of IL17 receptors

  • Cell-Based Therapies: Approaches to reduce pathogenic Th17 cells or enhance regulatory T cell function

• Potential Applications in Specific Diseases:

  • Immune-Mediated Hemolytic Anemia (IMHA): Evidence suggests IL17A contributes to disease pathogenesis, and levels remain elevated in non-surviving dogs , making it a logical therapeutic target

  • Canine Atopic Dermatitis: Given IL17A's role in epithelial inflammation and its synergy with allergen responses , IL17A blockade might benefit allergic skin diseases

  • Immune-Mediated Polyarthritis: Based on the success of IL17A inhibition in human inflammatory arthritis, similar approaches might benefit canine joint inflammation

  • Inflammatory Bowel Disease: IL17A's actions on intestinal epithelial cells suggest potential benefit in canine IBD

• Advantages of IL17A-Targeted Therapy:

  • Specificity: More targeted than broad immunosuppressants currently used in veterinary medicine

  • Preservation of Other Immune Functions: Unlike glucocorticoids or cyclosporine, IL17A inhibition would leave many protective immune mechanisms intact

  • Potential for Disease Modification: By targeting a key pathogenic pathway rather than just symptoms

  • Biomarker-Guided Therapy: Ability to monitor IL17A levels to guide treatment decisions and predict outcomes

• Implementation Considerations:

  • Patient Selection: IL17A levels could identify which dogs are most likely to benefit from targeted therapy

  • Combination Approaches: IL17A inhibition might work synergistically with existing therapies, potentially allowing dose reduction of broader immunosuppressants

  • Treatment Monitoring: Serial measurement of serum IL17A could provide an objective marker of treatment efficacy

  • Prophylactic Applications: In high-risk patients, early intervention targeting IL17A might prevent disease progression

• Translational Opportunities:

  • One Health Approach: Findings from canine IL17A-targeted therapies could inform human medicine and vice versa

  • Natural Disease Models: Dogs with spontaneous disease offer advantages over induced models for testing IL17A therapeutics

  • Comparative Efficacy: Studies comparing IL17A inhibition with established therapies would advance both veterinary and human medicine

• Complementary Approaches:

  • Vitamin D Supplementation: Evidence that calcitriol suppresses IL17A-induced inflammation in canine epithelial cells suggests vitamin D may be a simple adjunctive therapy

  • Microbiome Modulation: Targeting the microbiome to reduce factors that promote pathogenic Th17 responses

  • Dietary Interventions: Specific nutrients that may dampen IL17A-mediated inflammation

The development of IL17A-targeted therapies for canine diseases represents an exciting frontier in veterinary medicine, with potential to transform management of challenging autoimmune and inflammatory conditions while advancing our understanding of comparative immunology.

What are the most promising research questions regarding IL17A in canine health and disease for the next decade?

The next decade of research on IL17A in canine health and disease holds tremendous potential for breakthrough discoveries. The following represent the most promising and impactful research questions that merit investigation:

• Fundamental Biology and Regulation:

  • What is the complete transcriptional and epigenetic regulatory network controlling IL17A expression in canine immune cells?

  • How do canine-specific genetic variants influence IL17A production and signaling?

  • What is the detailed proteome of the IL17A signaling complex in different canine cell types?

  • How does the canine microbiome influence IL17A production and function in different tissues?

• Disease Mechanisms and Biomarkers:

  • Can a panel combining IL17A with other biomarkers more accurately predict outcomes in IMHA than IL17A alone ?

  • What role does IL17A play in canine autoimmune diseases beyond IMHA, such as immune-mediated thrombocytopenia, polyarthritis, and thyroiditis?

  • How does IL17A contribute to the pathogenesis of canine inflammatory skin diseases and allergic conditions?

  • Is there a causal relationship between IL17A and thrombotic complications in canine immune-mediated diseases?

• Therapeutic Development and Precision Medicine:

  • Can canine-specific anti-IL17A biologics be developed with favorable safety and efficacy profiles?

  • Which canine patients are most likely to benefit from IL17A-targeted therapies, and can predictive biomarkers be identified?

  • How does IL17A blockade compare to standard immunosuppressive protocols for canine autoimmune diseases in terms of efficacy, safety, and long-term outcomes?

  • Can small molecule inhibitors of IL17A signaling provide effective alternatives to biologics for canine applications?

• Translational and Comparative Research:

  • How do naturally occurring IL17A-driven diseases in dogs compare to their human counterparts at molecular and cellular levels?

  • Can spontaneous canine models accelerate the development of novel IL17A-targeting approaches for human medicine?

  • What are the key species-specific differences in IL17A biology that must be considered in translational research?

  • Can monitoring IL17A in pet dogs exposed to environmental factors help identify risks for human inflammatory diseases?

• Novel Biological Functions:

  • What is the role of IL17A in canine tissue repair and regeneration processes?

  • How does IL17A interact with the nervous system in canine neuroinflammatory conditions?

  • What role does IL17A play in canine cancer immunity, and could it be targeted in cancer immunotherapy?

  • How does aging affect IL17A production and function in dogs, and does this contribute to age-related diseases?

• Technology Development and Implementation:

  • Can point-of-care testing for IL17A be developed to guide clinical decision-making in veterinary practice?

  • How can advanced imaging techniques be applied to map IL17A-producing cells in canine tissues?

  • Can gene editing approaches targeting IL17A be safely applied in canine disease models?

  • What computational models best predict the impact of IL17A modulation in complex immune networks?

Addressing these research questions will not only advance our understanding of IL17A biology in dogs but also potentially transform approaches to canine immune-mediated diseases while yielding valuable insights for comparative medicine.