Myeloid NK-Cell Identification via CD11b Segmentation
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
The specific role of classic natural killer (NK)-cells in metaflammation, a chronic systemic low-grade immune activation contributing to metabolic syndrome, remains poorly defined, despite their significant presence in white adipose tissue and their contribution to obesity-associated insulin resistance.
Innovation Solution
Identification and characterization of a distinct subset of NK-cells, termed CD11b hi< NK-cells, which express myeloid marker genes and are critical in obesity and insulin resistance, along with the development of ex-vivo methods for determining and targeting these cells using specific markers like CD56, NKp46, IL6Ra, and Stat3 signaling.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional NK-cell markers (CD3-, CD56+, NKp46+) are used to identify NK-cells, then NK-cell population can be detected, but the specific subset of myeloid NK-cells involved in metaflammation cannot be distinguished
Solution Approach 1:
The patent segments the NK-cell population into distinct subsets by introducing the CD11b marker to differentiate myeloid NK-cells (CD11bhiCD56+NKp46+) from conventional NK-cells. This segmentation allows precise identification of the specific NK-cell subset involved in metaflammation without requiring complex multi-parameter analysis beyond standard flow cytometry capabilities.
Solution Approach 2:
The patent uses CD11b as an intermediary marker that bridges the gap between conventional NK-cell identification and myeloid cell characterization. This intermediary marker enables the detection of myeloid NK-cells using standard flow cytometry panels without requiring complex genetic or functional assays.
2Loss of information
If the role of NK-cells in metaflammation is studied using standard markers, then general NK-cell activation status can be assessed, but the specific contribution of myeloid NK-cells to obesity-associated inflammation remains undefined
Solution Approach 1:
The patent segments the NK-cell population into distinct subsets by introducing the CD11b marker to differentiate myeloid NK-cells (CD11bhiCD56+NKp46+) from conventional NK-cells. This segmentation allows precise identification of the specific NK-cell subset involved in metaflammation without requiring complex multi-parameter analysis beyond standard flow cytometry capabilities.
Solution Approach 2:
The patent changes the phenotypic parameters used to define NK-cells by incorporating CD11b expression levels. This parameter change enables the detection of myeloid NK-cells using standard flow cytometry panels without requiring complex genetic or functional assays.
3Reliability
If myeloid NK-cells are targeted for ablation to treat obesity and insulin resistance, then therapeutic efficacy is improved, but specificity of targeting must be ensured to avoid affecting conventional NK-cells
Solution Approach 1:
The patent applies local quality by using the specific CD11bhiCD56+NKp46+ phenotype to selectively identify and target only myeloid NK-cells. This localized targeting ensures that therapeutic interventions affect only the specific subset involved in metaflammation while preserving conventional NK-cell function.
Solution Approach 2:
The patent changes the phenotypic parameters used to define NK-cells by incorporating CD11b expression levels. This parameter change enables the detection of myeloid NK-cells using standard flow cytometry panels without requiring complex genetic or functional assays.
Data Source
Figure 1A
Figure 1B
Figure 1C
AI summary
The present invention relates to ex-vivo methods for determining myeloid NK-cells, methods for diagnosis of a disease associated with and/or caused by myeloid NK- cells as well as depletion of myeloid NK-cells for use in treating. The present is also related to methods for determining whether a candidate agent reduces a myeloid NK-cell population.