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American Physiological Society, American Journal of Physiology - Gastrointestinal and Liver Physiology, 5(323), p. G439-G460, 2022

DOI: 10.1152/ajpgi.00104.2022

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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

Journal article published in 2022 by Peter Flood, Jerzy A. Woznicki, Aine Fanning, Aileen Houston ORCID, Tadhg Crowley, Woznicki Ja, Andrea Christopher, Alessandra Vaccaro ORCID, Sheila McSweeney, Sarah Ross, Aileen Hogan, Elizabeth Brint ORCID, Agnieszka Skowyra, Syed A. Zulquernain, Milan Bustamante and other authors.
This paper was not found in any repository, but could be made available legally by the author.
This paper was not found in any repository, but could be made available legally by the author.

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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.