TL1A-activated T cells remodel the rectal mucosa in patients with Crohn's disease with perianal fistulising disease.

TL1A-activated T cells induce a distinct rectal mucosal signature in Crohn's disease patients with perianal fistulising disease, independent of inflammation and anti-TNF therapy.

• Why it matters: Understanding the cellular mechanisms driving fistula formation in Crohn's disease is crucial for developing targeted treatments, as current therapies often fail to address PFD specifically.
• What they did: Single-cell RNA sequencing of rectal biopsies from 31 patients with Crohn's disease with or without PFD revealed cellular and transcriptomic alterations driven by TL1A activation in CD4+ T cells, involving novel mediators like lymphotoxin beta and IL-22.
• The result: The study uncovers a TL1A-LTβ1β2/IL-22 axis active even during anti-TNF therapy, suggesting that targeting TL1A could offer new therapeutic avenues for PFD management.