Trained Immunity Contribution to Autoimmune and Inflammatory Disorders

Area of Science:

• Immunology
• Cellular Biology
• Genetics

Background:

• Autoimmune and autoinflammatory (AIF) disorders involve dysregulated immune responses to self-antigens.
• Monocytes and macrophages (Mo/Ma) are key innate immune cells implicated in both autoimmune and AIF diseases.
• The plasticity of Mo/Ma function complicates understanding their precise role in immune disorders.

Purpose of the Study:

• To explore the role of trained immunity in autoimmune and autoinflammatory diseases.
• To elucidate the metabolic and epigenetic mechanisms of trained immunity affecting Mo/Ma.
• To contrast the controversial evidence regarding trained immunity's impact on AIF and autoimmune conditions.

Main Methods:

• Review of scientific literature on trained immunity, Mo/Ma function, and epigenetic/metabolic reprogramming.
• Analysis of mechanisms including cellular metabolism shifts (e.g., glycolysis) and chromatin modification.
• Contrasting studies on the pro-inflammatory and anti-inflammatory effects of trained immunity.

Main Results:

• Trained immunity, mediated by Mo/Ma and NK cells, involves epigenetic and metabolic alterations leading to enhanced innate immune responses.
• Induction of trained immunity reprograms hematopoietic stem cells (HSCs), conferring a memory-like phenotype to Mo/Ma.
• Evidence suggests trained immunity can exacerbate autoimmune/AIF diseases through enhanced inflammation or offer protective anti-inflammatory effects.

Conclusions:

• Trained immunity's influence on autoimmune and autoinflammatory diseases is complex and debated.
• Metabolic and epigenetic reprogramming of Mo/Ma by trained immunity presents a potential therapeutic target.
• Further research is needed to reconcile conflicting findings and predict outcomes in AIF and autoimmune contexts.