Tissue-Specific Th17 Modulation via Segmentation
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Solution Overview
Problem
There is a need for a better understanding of the dynamic regulatory network that modulates and controls T cell balance, including Th17 cell differentiation, maintenance, and function, to develop therapeutic and diagnostic methods for autoimmune diseases.
Innovation Solution
The method involves contacting a population of T cells with agents that bind to or modulate the expression and activity of specific gene products, such as Cxcr6, AA467197, and Slamf6, to shift the balance of Th17 cells towards non-pathogenic or pathogenic states, using agents like small molecules, antibodies, or genetic modifying agents like CRISPR systems.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If Th17 cells are activated to clear fungal infections and maintain barrier functions, then immune defense capability is improved, but autoimmune tissue inflammation occurs
Solution Approach 1:
The patent segments Th17 cells into distinct subpopulations based on tissue-specific expression patterns (e.g., skin-homing Th17 cells expressing CCR10, gut-homing Th17 cells expressing CCR6). This segmentation allows selective targeting of pathogenic Th17 cells in specific tissues while preserving protective Th17 cells in other locations, thereby maintaining immune defense capability while reducing autoimmune inflammation.
Solution Approach 2:
The patent applies local quality by developing tissue-specific therapeutic agents that target Th17 cells only in affected tissues. For example, topically administered agents target skin-homing Th17 cells in psoriasis, while orally administered agents target gut-homing Th17 cells in IBD. This localized approach reduces systemic immune suppression while treating tissue-specific autoimmune conditions.
2Object-generated harmful factors
If broad immune suppression is used to treat autoimmune diseases, then autoimmune inflammation is reduced, but susceptibility to infections increases
Solution Approach 1:
The patent segments the immune system response by targeting only pathogenic Th17 cell subpopulations in affected tissues rather than suppressing all immune responses. This selective approach preserves the function of protective Th17 cells and other immune cells needed for pathogen defense, thereby reducing autoimmune inflammation without increasing infection susceptibility.
Solution Approach 2:
The patent uses tissue-specific homing receptors (e.g., CCR6, CCR10) and their ligands as intermediaries to deliver therapeutic agents selectively to inflamed tissues. This intermediary mechanism enables precise targeting of pathogenic Th17 cells at the disease site while leaving the rest of the immune system intact and functional for pathogen defense.
3Object-generated harmful factors
If current Th17 cell targeting therapies are used, then autoimmune symptoms are alleviated, but tissue-specific pathogenicity is not adequately addressed
Solution Approach 1:
The patent segments Th17 cells into tissue-specific subpopulations (skin-homing, gut-homing, lung-homing, etc.) based on their expression of specific chemokine receptors and adhesion molecules. This segmentation enables the development of tailored therapies for different autoimmune conditions affecting specific tissues, thereby improving therapeutic precision and adaptability to tissue-specific pathogenicity.
Solution Approach 2:
The patent implements local quality by matching therapeutic agents to specific tissue contexts. For example, agents targeting CCR10-expressing Th17 cells are used for skin conditions like psoriasis, while agents targeting CCR6-expressing Th17 cells are used for gut conditions like IBD. This tissue-matched approach enhances therapeutic precision and addresses tissue-specific pathogenicity effectively.
Data Source
AI summary
The subject matter disclosed herein is generally directed to tissue specific modulation of Th17 differentiation and pathogenicity by targeting tissue specific Th17 gene programs and gene targets. The tissue specific modulation may be used therapeutically to treat a disease or condition in the tissue where it arises. The subject matter disclosed herein is also directed to detecting tissue specific Th17 cells for diagnostic and therapeutic methods.