AhR Ligands for Tr1 Cell Differentiation in Autoimmune Suppression
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Solution Overview
Problem
Current immune-suppressing drug therapies for autoimmune diseases, such as type 1 diabetes and graft versus host disease, cause severe side effects like increased infection risk and cancer due to nonspecific inhibition of cellular proliferation, failing to provide long-term remission without toxicity.
Innovation Solution
Development of non-toxic aryl hydrocarbon receptor (AhR) ligands that induce the differentiation of Tr1 cells to suppress pathogenic immune responses, using compounds like 10- and 11-chloro-7H-benzimidazo[2,1-albenzo[de]-Isoquinolin-7-one to activate AhR, promoting targeted T cell differentiation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional immune-suppressing drug therapies are used to treat autoimmune diseases, then immune suppression is achieved, but severe side effects occur including increased infection risk and cancer
Solution Approach 1:
The invention segments the immune system response by specifically targeting T cell differentiation pathways rather than suppressing all immune cells. The AhR ligands selectively induce Tr1 cell differentiation from T cells, creating a segmented approach that suppresses pathogenic immune responses while preserving other immune functions, thereby reducing side effects like infection risk and cancer susceptibility.
Solution Approach 2:
The invention applies local quality by directing immune suppression to specific cell types (T cells differentiating into Tr1 cells) rather than applying global suppression to all immune cells. The AhR ligands specifically modulate T cell differentiation pathways, creating localized immune suppression at the molecular and cellular level while maintaining overall immune system integrity and reducing harmful side effects.
2Object-generated harmful factors
If nonspecific immune suppression is applied to treat autoimmune diseases, then pathogenic immune responses are reduced, but long-term remission cannot be achieved without severe side effects
Solution Approach 1:
The invention introduces an intermediary mechanism by using AhR ligands as mediators to induce Tr1 cell differentiation. These Tr1 cells then act as intermediary regulatory cells that actively suppress pathogenic immune responses through physiological mechanisms. This intermediary approach creates sustained immune regulation without the need for continuous high-dose immunosuppression, enabling long-term remission with reduced side effects.
Solution Approach 2:
The invention changes the parameter of immune cell differentiation by using AhR ligands to shift T cell differentiation toward the Tr1 regulatory phenotype. This parameter change in cell fate determination creates a durable immunoregulatory effect, as differentiated Tr1 cells provide ongoing suppression of pathogenic responses, achieving long-term remission without severe side effects associated with conventional immunosuppression.
3Object-generated harmful factors
If T cell differentiation is specifically targeted through AhR activation, then pathogenic immune responses are suppressed, but the complexity of the therapeutic approach increases
Solution Approach 1:
The invention employs self-service by utilizing the body's own AhR signaling pathways and natural T cell differentiation mechanisms to achieve immune suppression. The AhR ligands work with endogenous cellular machinery to induce Tr1 cell differentiation, leveraging existing biological systems rather than requiring complex external intervention. This self-service approach reduces therapeutic complexity while maintaining effectiveness in suppressing pathogenic T cell responses.
Data Source
AI summary
Small molecule AhR ligands are disclosed. The ligands can induce the differentiation of Tr1 cells to suppress pathogenic immune responses without inducing nonspecific immune suppression. Methods of treatment of autoimmune diseases using the AhR ligands are also disclosed.