JAK and TYK2 inhibitors differentially modulate interferon/TNF-driven inflammation, stemness and proliferation in the colonic epithelium of ulcerative colitis

What To Know

This preprint reports laboratory experiments using colonic intestinal epithelial organoids derived from UC patients plus biopsy staining, examining how several JAK and TYK2 inhibitors affect epithelial signaling, gene expression, and proliferation when exposed to interferons and TNF.

The study compared multiple JAK inhibitors (tofacitinib, upadacitinib, filgotinib) and TYK2 inhibitors (brepocitinib, deucravacitinib), finding that upadacitinib broadly reduced interferon- and interferon+TNF-driven inflammatory gene networks and chemokine secretion, while TYK2-selective deucravacitinib showed more selective effects (notably under IFNλ1 stimulation).

The authors also note increased epithelial proliferation (Ki67) in biopsies from patients treated with JAK inhibitors. The work is lab-based (organoids, transcriptomics, protein assays) and uses patient-derived tissues and clinical biopsies to connect findings to human UC tissue.

It helps clarify direct epithelial effects of these drugs rather than immune-cell mediated actions. This is a preprint (openRxiv) presenting mechanistic and transcriptomic data; it does not report clinical outcomes.

It can inform hypotheses about how different JAK/TYK2 inhibitors might affect mucosal healing or epithelial biology but does not replace clinical trial evidence. If you are considering treatment changes, discuss with your GI clinician—this study does not provide guidance on prescribing or comparative effectiveness for individual patients.