Lactobacillus Plantarum ST Peptide Modulates Dendritic Cells

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Solution Overview

Problem

Current treatments for inflammatory diseases and autoimmune disorders related to intestinal microbiota dysregulation and compromised oral tolerance lack effective immunomodulating and anti-inflammatory solutions.

Innovation Solution

A peptide with a specific amino acid sequence, derived from Lactobacillus plantarum, modulates dendritic cells to block pro-inflammatory cytokines and enhance anti-inflammatory cytokines, promoting intestinal homeostasis by inducing a regulatory phenotype and secondary migration of T lymphocytes away from the gastrointestinal tract.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional treatments are used for inflammatory diseases, then symptom management is attempted, but effective immunomodulating and anti-inflammatory solutions are lacking

Engineering Contradiction:
Improveeffectiveness of treatmentVSAvoidinflammation and immune dysregulation
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The ST peptide acts as an intermediary molecule that mediates between the immune system and inflammatory responses. It specifically modulates dendritic cell function and cytokine production, serving as a bridge to restore immune homeostasis without directly suppressing all immune activity. The peptide binds to specific receptors on dendritic cells to regulate IL-12 and IL-10 production.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention changes the immunological parameters of the system by introducing a peptide that specifically alters cytokine production ratios. It shifts the balance from pro-inflammatory (IL-12) to anti-inflammatory (IL-10) cytokines, thereby changing the overall immune response parameters from inflammatory to homeostatic.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If the immune system reacts against intestinal microbiota, then inflammatory processes develop, but oral tolerance mechanism fails

Engineering Contradiction:
Improveoral toleranceVSAvoidinflammatory processes
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The ST peptide serves as an intermediary that restores the oral tolerance mechanism by modulating dendritic cell responses to microbial antigens. It enables dendritic cells to properly regulate immune responses to intestinal microbiota, preventing inappropriate inflammatory reactions while maintaining immune surveillance.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

Instead of trying to suppress the immune system's reactivity to microbiota, the invention inverts the approach by enhancing the regulatory functions of dendritic cells. It reverses the pathological response pattern by promoting anti-inflammatory cytokine production and regulatory T cell differentiation, thereby restoring tolerance rather than merely blocking inflammation.

Inventive Principle:
Principle #13The other way round (Inversion)

3Reliability

If dendritic cells produce pro-inflammatory cytokines, then immune response is activated, but intestinal homeostasis is lost

Engineering Contradiction:
Improveintestinal homeostasisVSAvoidpro-inflammatory cytokines
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The ST peptide changes the cytokine production parameters of dendritic cells by specifically downregulating IL-12 and upregulating IL-10. This parameter shift transforms the dendritic cell from a pro-inflammatory state to an anti-inflammatory, homeostatic state, thereby restoring intestinal balance.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention introduces a feedback mechanism where the ST peptide binds to dendritic cells and regulates their cytokine production in a controlled manner. This creates a negative feedback loop that prevents excessive pro-inflammatory responses while maintaining appropriate immune surveillance, thereby preserving homeostasis.

Inventive Principle:
Principle #23Feedback

Data Source

PatentEP2754666B1Peptide secreted by lactobacillus plantarum with immunomodulating function
Publication Date: 2019.12.18 IMPERIAL COLLEGE INNVOATIONS LTD
  • EP2754666B1 patent drawingFigure 1~2B
  • EP2754666B1 patent drawingFigure 5a~5b
  • EP2754666B1 patent drawingFigure 6~7

AI summary

Among the fewer than 10 proteins primarily secreted by the species Lactobacillus plantarum, there is one of 30 kDa that contains an internal fragment without cleavage sites for the most important intestinal proteases and characterized by having a serine and threonine content of at least 50%. The genetic information encoded in this fragment, designated ST peptide, has been used for producing and purifying said peptide, thus making it possible to conduct various tests in vitro. To summarize, the ST peptide is considered to promote the process of immunologic ignorance of our gastrointestinal immune system toward the commensal bacteria of our gastrointestinal tract, thus favoring the mechanisms of oral tolerance. Therefore the ST peptide could be used in immunotherapy, especially in the context of certain autoimmune diseases and certain inflammatory diseases.