Unveiling the TL1A-LTα1β2/IL-22 Axis: A New Therapeutic Target in Crohn’s Disease with Perianal Fistulising Disease

Highlight

• 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.

Study Background