Innate Lymphoid Cell State Modulation for Psoriasis Control
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Solution Overview
Problem
The factors balancing homeostatic and pathological ILC responses are unclear, and distinguishing homeostatic from pro-inflammatory ILCs is challenging due to the lack of known markers, leading to conditions like psoriasis and inflammatory bowel disease.
Innovation Solution
Administer agents capable of shifting ILCs between different functional states, such as preventing naïve/quiescent ILCs from becoming type 2 ILCs or promoting shifts to ILC3-like cells, using small molecules, genetic modifying agents like CRISPR systems, and modulating gene expression or activity of specific genes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If agents are administered to shift ILCs between functional states, then inflammatory and autoimmune responses are reduced or prevented, but the complexity of treatment and mechanism understanding increases
Solution Approach 1:
The patent applies parameter changes by modulating the functional state of ILCs through agents that alter gene expression profiles and cellular differentiation pathways. Specifically, the agents shift ILCs from pathogenic states (ILC2/ILC3-like) to homeostatic states (naïve/quiescent) by changing expression levels of key transcription factors and cytokines, thereby resolving the technical contradiction between achieving reliable disease control and managing treatment complexity
Solution Approach 2:
The patent employs intermediary molecules (agents) that mediate the transition of ILCs between functional states. These agents act as intermediaries by binding to specific targets on or in ILCs, triggering intracellular signaling cascades that ultimately shift the cellular state. This intermediary approach allows for controlled modulation of ILC function while providing a manageable treatment mechanism
2Measurement precision
If markers are developed to distinguish homeostatic from pro-inflammatory ILCs, then diagnostic precision improves, but the complexity of identification and characterization increases
Solution Approach 1:
The patent applies segmentation by dividing the continuous spectrum of ILC states into distinct, marker-defined categories. By identifying specific gene expression profiles and surface markers that characterize naïve/quiescent versus ILC2/ILC3-like states, the patent creates discrete segments that can be detected and measured. This segmentation approach transforms the continuous differentiation spectrum into measurable, distinguishable states, resolving the contradiction between diagnostic precision and detection difficulty
Solution Approach 2:
The patent employs molecular 'color changes' by using gene expression markers and protein markers as indicators of ILC state. Different marker expression patterns serve as molecular signatures that indicate whether an ILC is in a homeostatic or pro-inflammatory state, enabling precise detection and characterization through standardized molecular assays
Data Source
AI summary
The subject matter disclosed herein is generally directed to methods and compositions for modulating inflammation driven by differentiation of quiescent tissue-resident ILCs into a spectrum of pathogenic effectors. The subject matter disclosed herein is also generally directed to detecting and monitoring an ILC response. Additionally, the subject matter is directed to treating skin inflammation, such as psoriasis.