Published in
American Physiological Society, American Journal of Physiology - Gastrointestinal and Liver Physiology, 5(323), p. G439-G460, 2022
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DNA sensor-associated type I interferon signaling is increased in ulcerative colitis and induces JAK-dependent inflammatory cell death in colonic organoids
,
Tadhg Crowley,
Woznicki Ja,
Andrea Christopher,
Alessandra Vaccaro ,
Sheila McSweeney,
Sarah Ross,
Aileen Hogan,
Elizabeth Brint ,
Agnieszka Skowyra,
Syed A. Zulquernain,
Milan Bustamante
and other authors.
Full text: Unavailable
Abstract
This study found that patients with active UC have significantly increased colonic gene expression of cytosolic DNA sensor, inflammasome, STING, and type I IFN signaling pathways. The type I IFN, IFN-β, in combination with TNF-α induced JAK-dependent but NLRP3 and inflammasome-independent inflammatory cell death of colonic organoids. This novel inflammatory cell death phenotype is relevant to UC immunopathology and may partially explain the efficacy of the JAKinibs tofacitinib and upadacitinib in patients with UC.