Investigating endogenous immune-mediated monocyte memory in rheumatoid arthritis

Area of Science:

• Immunology
• Cellular Biology
• Epigenetics

Background:

• Inflammation must be controlled to protect against danger without harming healthy tissues.
• Innate memory plays a crucial role in balancing protective and destructive inflammatory responses.

Purpose of the Study:

• To assess the contribution of innate memory to the control of inflammation.
• To compare innate memory evoked by endogenous (tenascin-C) versus pathogenic (LPS) stimuli.

Main Methods:

• Transcriptomic and epigenetic profiling of monocytes and macrophages.
• Comparison of responses to tenascin-C and LPS in healthy individuals and rheumatoid arthritis (RA) patients.

Main Results:

• Tenascin-C reprograms monocytes, causing both suppressed and enhanced responses to subsequent challenges.
• Endogenous triggers induce trained responses not seen with LPS, including genes linked to RA pathology.
• RA cells show epigenetic alterations associated with heightened inflammatory gene expression.

Conclusions:

• Innate reprogramming by endogenous triggers contributes to chronic inflammation in sterile diseases.
• Unique pathways activated by endogenous triggers offer potential for targeted interventions in RA.
• Findings suggest novel therapeutic strategies for RA without causing global immune suppression.