Regulatory circuits that build and sustain noninfectious granulomas.

Regulatory circuits linking immune cells, metabolism, and stroma sustain noninfectious granulomas across diverse diseases.

• Why it matters: Persistent inflammation in granulomatous diseases disrupts tissue architecture and impairs organ function, highlighting the need to understand how these lesions are maintained.
• What they did: The authors synthesize recent studies to move beyond linear cytokine models and propose that granulomas are maintained by reinforcement among local immune, metabolic, and stromal programs, with comparisons across diseases like sarcoidosis to identify conserved mechanisms.
• The result: Defining these regulatory circuits may enable strategies to dismantle established granulomatous lesions and improve disease management.