Urate-induced immune programming: Consequences for gouty arthritis and hyperuricemia

Area of Science:

• Immunology
• Metabolic Disorders
• Rheumatology

Background:

• Trained immunity involves innate immune cell reprogramming, enhancing responses but risking chronic inflammation.
• Gout features persistent inflammation and comorbidities, with hyperuricemia as a key risk factor.
• Hyperuricemia is linked to various inflammatory diseases, suggesting urate's broader impact.

Purpose of the Study:

• To review evidence linking hyperuricemia to systemic inflammation in gout.
• To explore urate-induced transcriptional and epigenetic reprogramming of myeloid cells.
• To discuss urate's role in innate immune memory and potential therapeutic targets.

Main Methods:

• Review of experimental and observational studies on urate, inflammation, and immune cell function.
• Analysis of transcriptional and epigenetic changes in monocytes and macrophages.
• Discussion of in vitro and in vivo data on urate's inflammatory effects.

Main Results:

• Urate alters myeloid cell inflammatory capacity, promoting enhanced responsiveness.
• Evidence suggests urate induces epigenetic reprogramming, leading to maladaptive immune responses.
• Soluble urate and monosodium urate crystals contribute to inflammation and innate immune memory.

Conclusions:

• Hyperuricemia is a significant driver of chronic systemic inflammation in gout.
• Urate acts as a metabolite inducing innate immune memory, impacting monocyte and macrophage function.
• Understanding urate's role may reveal new therapeutic strategies for gout and its comorbidities.