Trained immunity in autoinflammatory diseases: Cellular reprogramming across the monogenic-polygenic spectrum

Area of Science:

• Immunology
• Epigenetics
• Metabolic reprogramming

Background:

• Trained immunity is an innate immunological memory involving epigenetic and metabolic changes.
• It enhances innate immune cell responses, contributing to chronic inflammation and autoinflammatory diseases.
• Unlike adaptive immunity, trained immunity affects innate cells and their progenitors.

Purpose of the Study:

• To review evidence linking trained immunity to monogenic and polygenic autoinflammatory diseases.
• To explore the role of trained immunity in various inflammatory conditions.
• To identify knowledge gaps and potential therapeutic strategies.

Main Methods:

• Narrative review of existing scientific literature.
• Synthesis of evidence on trained immunity in monogenic and polygenic autoinflammatory diseases.
• Analysis of data on epigenetic and metabolic reprogramming in immune cells.

Main Results:

• Strong evidence links trained immunity to mevalonate kinase deficiency.
• Moderate evidence supports its role in familial Mediterranean fever, cryopyrin-associated periodic syndromes, and TNF receptor-associated periodic syndrome.
• Convincing evidence shows its involvement in polygenic disorders like gout, atherosclerosis, obesity, and type 2 diabetes, with growing evidence in other inflammatory diseases.

Conclusions:

• Autoinflammatory diseases may result from an interplay between genetic predisposition and dysfunctional innate immune memory.
• Further research is needed on progenitor cell reprogramming, disease-specific epigenetic markers, and reversibility of trained states.
• Targeting abnormal innate immune memory could lead to novel therapeutic approaches.