Immunosuppressive Dendritic Cells via IL-27 and CD39 Axis
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Solution Overview
Problem
Current treatments for autoimmune diseases, such as multiple sclerosis and type 1 diabetes, are inadequate in modulating dendritic cell activity to effectively suppress autoimmune responses, as they fail to adequately regulate the activation and differentiation of T cells, leading to persistent inflammation and tissue damage.
Innovation Solution
The development of immunosuppressive dendritic cells through activation of the IL-27/CD39 axis, which involves contacting dendritic cells with IL-27 or CD39 agonists to upregulate CD39 expression, reduce ATP levels, and inhibit the NLRP3 inflammasome, thereby promoting regulatory T cell generation and suppressing effector T cell differentiation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional treatments are used for autoimmune diseases, then general immune suppression may be achieved, but dendritic cell activity is not adequately modulated to effectively suppress autoimmune responses
Solution Approach 1:
The patent changes the functional parameters of dendritic cells by activating the IL-27/CD39 axis, which upregulates CD39 expression and alters ATP metabolism. This parameter change in dendritic cell activity enables effective suppression of autoimmune responses without requiring complex treatment protocols
Solution Approach 2:
The patent introduces the IL-27/CD39 axis as an intermediary mechanism between dendritic cells and T cells. CD39 acts as a mediator that converts ATP to adenosine, creating an immunosuppressive microenvironment that effectively suppresses autoimmune responses through a controlled intermediate step rather than direct complex intervention
2Reliability
If dendritic cells are activated to suppress autoimmune responses, then regulatory T cell generation is promoted, but pro-inflammatory responses may persist
Solution Approach 1:
The patent converts the harmful pro-inflammatory signaling through ATP and NLRP3 inflammasome activation into a beneficial immunosuppressive response. By upregulating CD39, the system metabolizes ATP to adenosine, transforming a pro-inflammatory signal into an anti-inflammatory one that promotes regulatory T cell generation while suppressing effector T cell differentiation
Solution Approach 2:
The patent applies preliminary anti-action by activating the IL-27/CD39 axis before autoimmune responses fully develop. This pre-emptive activation of immunosuppressive dendritic cells prevents the full development of pro-inflammatory responses and promotes regulatory T cell generation in advance, counteracting potential harm before it occurs
3Reliability
If current treatments fail to regulate T cell activation and differentiation, then autoimmune responses persist, but increasing treatment intensity may cause excessive immune suppression
Solution Approach 1:
The patent applies local quality by selectively modulating dendritic cell function through the IL-27/CD39 axis rather than globally suppressing the entire immune system. This localized intervention specifically affects dendritic cell-T cell interactions and ATP metabolism in immune synapses, achieving precise T cell response regulation without excessive broad immune suppression
Solution Approach 2:
The patent introduces dynamics by creating a responsive immunosuppressive mechanism that adapts to autoimmune conditions. The activated dendritic cells dynamically regulate T cell responses based on local ATP levels and inflammatory signals, providing flexible control that prevents both persistent inflammation and excessive immune suppression
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach effectively generates immunosuppressive dendritic cells that can be used to treat autoimmune diseases by reducing pro-inflammatory responses and promoting anti-inflammatory cytokine production, thereby inhibiting the progression of autoimmune diseases like multiple sclerosis and type 1 diabetes.
Implementation Method 1
interleukin 27 (IL-27) acts on dendritic cells (DCs) to expand regulatory T cells (Tregs) and/or suppress T cell response
Implementation Method 2
CD39 expressed by conventional DCs (cDCs) reduced the extracellular concentration of ATP (eATP)
Implementation Method 3
the immunosuppressive effects of IL-27 on DCs are mediated at least in part through induction of the immunoregulatory molecule ectonucleotidase CD39 expression in DCs
Implementation Method 4
decreased ATP-triggered activation of the NLRP3 inflammasome
Data Source
AI summary
Embodiments of various aspects described herein are directed to methods and compositions for producing a tolerognic or immunosuppressive dendritic cell. In particular, an immunosuppressive dendritic cell can be produced by contacting a dendritic cell with an agent that stimulates the IL 27/ectonucleotidase CD39 axis signaling. In some embodiments, the methods and/or compositions described herein can be used for treating an autoimmune disease or disorder, e.g., but not limited to multiple sclerosis (MS) and type 1 diabetes.