PI16 Biomarker for Regulatory T Cell Isolation Specificity
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Solution Overview
Problem
Current methods lack effective markers for isolating and detecting regulatory T (Treg) cells, which are crucial for autoimmune disease treatment and immune response modulation, due to insufficient cell surface markers, hindering diagnostic and therapeutic strategies.
Innovation Solution
The use of nucleic acid and protein markers such as PI16, IL1R1, PKD1L3, PTPRB, CD146, AQP3, RGMB, CD49f, PERP, and LSR to detect and isolate Treg cells, allowing for their enrichment and potential therapeutic manipulation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If traditional T cell markers (CD4, CD25) are used to identify Treg cells, then Treg cells can be partially selected, but the specificity is insufficient and other T cell populations cannot be effectively distinguished
Solution Approach 1:
The patent segments the Treg cell detection process into multiple independent detection steps using different marker combinations. Instead of relying on a single complex marker, the invention divides the identification into sequential assessments of CD4, CD25, and FoxP3 expression, allowing each marker to be evaluated independently for more precise cell population discrimination
Solution Approach 2:
The patent introduces FoxP3 as an intermediary marker that mediates between the surface markers CD4 and CD25 and the definitive identification of Treg cells. FoxP3 serves as a functional mediator that confirms true Treg cell identity, resolving the ambiguity that arises when using only surface markers that may be expressed on non-Treg cell populations
2Measurement precision
If multiple marker combinations are used to improve Treg cell detection accuracy, then detection precision improves, but the complexity of the detection method increases
Solution Approach 1:
The patent employs dynamic detection strategies where the combination of markers used can be adjusted based on the specific experimental needs and cell population being analyzed. The method allows flexible pairing of surface markers (CD4+CD25+) with intracellular markers (FoxP3) depending on the required detection sensitivity and available resources
Solution Approach 2:
The patent adds a temporal dimension to the detection process by separating surface marker detection (CD4, CD25) from intracellular marker detection (FoxP3). This dimensional separation allows each marker type to be optimized independently - surface markers for initial enrichment and intracellular markers for definitive identification - thereby improving overall accuracy without requiring all markers to function simultaneously in a single complex assay
3Measurement precision
If FoxP3 is used as a marker for Treg cells, then specific identification is achieved, but the marker cannot be used for isolating viable Treg cells since it is an intracellular protein
Solution Approach 1:
The patent uses surface markers CD4 and CD25 to perform preliminary enrichment of Treg cells before applying the more specific but operationally challenging FoxP3 marker. This preliminary action creates a pre-enriched population that reduces the complexity of subsequent FoxP3-based isolation steps, making the overall process more feasible while maintaining high specificity
Solution Approach 2:
The patent implements a nested detection strategy where surface marker detection (CD4+CD25+) serves as an outer layer for initial selection, and intracellular FoxP3 detection serves as an inner layer for definitive identification. This nested approach allows the simpler surface marker assay to handle the bulk of the isolation task, while the more complex FoxP3 assay focuses on confirming true Treg cell identity in the pre-enriched population
Data Source
Figure 1A~1B
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AI summary
The invention of the present application is to markers of regulatory T (Treg) cells, in particular, cell surface markers of Peptidase Inhibitor 16 (PI16; SEQ ID NO: 27 & 28) and uses of those markers or compounds that bind thereto to identify or isolate Treg cells or to diagnose/prognose/treat/prevent Treg-mediated conditions. The present invention also provides methods for identification and/or isolation of Treg cell subpopulations and such isolated populations of Treg cells.