Gasdermin E Marker for IL-1α-Producing Th17 Cell Detection
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Solution Overview
Problem
Current methods fail to effectively identify and diagnose the status of Th17 cells in inflammatory diseases, particularly those exacerbated by IL-1α producing Th17 cells, and lack treatments that selectively inhibit their pro-inflammatory activity.
Innovation Solution
A method for diagnosing inflammatory diseases by detecting gasdermin E protein expression in IL-1α producing Th17 cells, and a method for identifying anti-inflammatory compounds by inhibiting gasdermin E protein pore formation, using assays that include contacting candidate compounds with gasdermin E protein or expressing gasdermin E in cells to detect assembly/pore formation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If current diagnostic methods are used to identify Th17 cells, then general Th17 cell detection is possible, but accurate identification of IL-1α producing Th17 cells cannot be achieved
Solution Approach 1:
The patent segments the Th17 cell population by introducing a specific marker (gasdermin E expression) to identify the pathogenic IL-1α producing subset. This segmentation allows precise differentiation between general Th17 cells and the specific pathogenic subset, resolving the contradiction between detection accuracy and method complexity by providing a targeted molecular marker.
Solution Approach 2:
The patent uses gasdermin E protein expression as an intermediary marker to indirectly identify IL-1α producing Th17 cells. Instead of directly detecting IL-1α production, the method employs gasdermin E as a surrogate marker that correlates with IL-1α producing capability, simplifying the diagnostic approach while maintaining accuracy.
2Object-affected harmful factors
If broad anti-inflammatory treatments are applied, then general inflammation is reduced, but selective inhibition of IL-1α producing Th17 cell activity cannot be achieved
Solution Approach 1:
The patent applies the local quality principle by developing compounds that specifically target the gasdermin E pathway in IL-1α producing Th17 cells. This allows selective inhibition of pro-inflammatory activity in the pathogenic subset while preserving the function of other T cell populations and anti-inflammatory Th17 cells, achieving both effectiveness and selectivity.
Solution Approach 2:
The patent employs parameter changes by modifying the inflammatory response parameters through selective inhibition of gasdermin E-mediated pyroptosis. This changes the specific parameter of IL-1α production and pyroptotic cell death in pathogenic Th17 cells without broadly suppressing all inflammatory pathways, enabling targeted therapeutic intervention.
3Object-generated harmful factors
If gasdermin E protein pore formation is inhibited, then pyroptosis and IL-1α release are reduced, but understanding of the mechanism is required
Solution Approach 1:
The patent replaces direct measurement of the mechanical pore formation process with biochemical assays that detect gasdermin E protein levels, cleavage patterns, and downstream effects. This substitution makes the mechanism detectable and measurable using standard laboratory techniques rather than requiring direct observation of pore formation.
Solution Approach 2:
The patent uses intermediate markers such as gasdermin E cleavage products and downstream pyroptotic markers as mediators to indirectly measure pore formation activity. These intermediaries provide measurable proxies for the difficult-to-detect pore formation process, enabling mechanism detection through standard biochemical methods.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Enables accurate diagnosis of inflammatory diseases caused by IL-1α producing Th17 cells and identifies effective anti-inflammatory compounds to treat these conditions, providing targeted therapeutic interventions.
Implementation Method 1
Gasdermines (GSDMs) are a family of intracellular proteins that execute pyroptosis. While GSDMs are expressed as inactive forms, certain proteases proteolytically activate them. The N-terminal fragments of GSDMs form pores in the plasma membrane, leading to osmotic cell lysis.
Implementation Method 2
The N-terminal fragments of GSDMs form pores in the plasma membrane, leading to osmotic cell lysis.
Implementation Method 3
While GSDMs are expressed as inactive forms, certain proteases proteolytically activate them.
Implementation Method 4
IL-1 cytokines, of which IL-1α and IL-1β, represent the most prominent members, exert profound inflammation upon binding to their shared IL-1R1 receptor
Data Source
AI summary
The present invention relates to a method, in particular an in vitro method, for diagnosing an inflammatory disease in a human patient, comprising detecting IL-1α producing Th17 cells in a sample comprising T cells obtained from said patient comprising detecting gasdermin E protein expression, wherein the presence of said IL-1α producing Th17 cells is indicative for an inflammatory disease in the human patient. The inflammatory disease is selected from the group of an inflammation that is caused or exacerbated by IL-1α producing Th17 cells, inflammation caused or related to danger signal IL-1α. The present invention further relates to methods for diagnosing the status of an inflammatory disease in a human patient, or for identifying an inflammation modulating compound, such as an anti-inflammatory compound. Furthermore, the present invention relates to a kit for performing the above methods. Finally, improved inflammation modulating, and in particular anti-inflammatory compounds or pharmaceutical compositions are provided.