Re-search: neutrophils, NETs, and autoimmunity in ulcerative colitis
Re-search: neutrophils, NETs, and autoimmunity in ulcerative colitis; When the body's defenders become attackers
Ulcerative colitis strikes mostly in adulthood, causing the immune system to attack the gut with painful wounds and bleeding that comes and goes unpredictably. Five million people worldwide live with this disabling disease that can lead to severe complications which can cause death, including colon cancer. Doctors don't know what triggers it, and while treatments can reduce inflammation and ease symptoms, they don't cure the disease—it keeps coming back.
I focused on neutrophils—white blood cells that normally protect us by casting sticky web-like traps to catch bacteria. My research questioned whether these traps backfire in ulcerative colitis: instead of protecting the gut, they damage it and trigger the body to attack its own tissue.
I investigated whether patients' immune systems mistake these traps for threats and launch attacks against them. This creates a vicious cycle: neutrophils try to help, the body attacks their traps, inflammation spreads, more neutrophils arrive, and the cycle repeats. I studied blood and tissue from patients to track these immune responses and tested whether common medications could break this cycle.
This thesis of Erick Mendieta Escalante confirmed the "friendly fire" theory: many patients' immune systems do attack their own neutrophil traps, preventing cleanup and feeding continuous inflammation. We discovered that mesalamine—a standard medication for the disease—works by stopping neutrophils from forming these traps in the first place, preventing the friendly fire from starting.
Understanding this self-destructive cycle helps solve the mystery of what causes the disease and opens paths to create new treatments that could help millions of lives by finding a more definitive cure.