Identification of a unique cellular and transcriptomic signature in the rectal mucosa of Crohn’s disease patients with perianal fistulising disease (PFD).
TL1A-activated CD4+ T cells induce a novel inflammatory axis involving lymphotoxin beta (LTB/LTα1β2) and interleukin-22 (IL-22), remodeling rectal fibroblasts and epithelial cells.
This TL1A-LTα1β2/IL-22 pathway operates independently of TNF signaling, remaining active despite anti-TNF therapy, suggesting alternative therapeutic targets.
The findings substantiate TL1A inhibition as a promising strategy in managing PFD, a severe complication of Crohn’s disease.
