DNA sensor-associated type I interferon signaling is increased in ulcerative colitis and induces JAK-dependent inflammatory cell death in colonic organoids-Reference-Cited by-同舟云学术

DNA sensor-associated type I interferon signaling is increased in ulcerative colitis and induces JAK-dependent inflammatory cell death in colonic organoids

Published:2022-11-01 Issue:5 Volume:323 Page:G439-G460
ISSN:0193-1857
Container-title:American Journal of Physiology-Gastrointestinal and Liver Physiology
language:en
Short-container-title:American Journal of Physiology-Gastrointestinal and Liver Physiology

Author:

Flood Peter¹,Fanning Aine¹,Woznicki Jerzy A.¹,Crowley Tadhg¹,Christopher Andrea¹,Vaccaro Alessandra¹^ORCID,Houston Aileen¹²,McSweeney Sheila¹,Ross Sarah¹,Hogan Aileen¹,Brint Elizabeth¹³,Skowyra Agnieszka¹,Bustamante Milan¹,Ambrose Monica¹,Moloney Gerard¹^ORCID,MacSharry John¹⁴⁵,Hammarström Marie-Louise⁶,Hurley Margot¹²,Fitzgibbons Christine¹,Quigley Eamonn M. M.¹,Shanahan Fergus¹²,Zulquernain Syed A.¹²,McCarthy Jane⁷,Dodson G. Steven⁸,Dabbagh Karim⁸,McRae Bradford L.⁹,Melgar Silvia¹,Nally Ken¹¹⁰^ORCID

Affiliation:

1. APC Microbiome Ireland, University College Cork, Cork, Ireland

2. Department of Medicine, University College Cork, Cork, Ireland

3. Department of Pathology, Cork University Hospital, University College Cork, Clinical Sciences Building, Cork, Ireland

4. School of Microbiology, University College Cork, Cork, Ireland

5. School of Medicine, University College Cork, Cork, Ireland

6. Section of Infection and Immunology, Department of Clinical Microbiology, Umeå University, Umeå, Sweden

7. Department of Gastroenterology, Mercy University Hospital, Cork, Ireland

8. Second Genome, Brisbane, California

9. Immunology Discovery, Abbvie Bioresearch Center, Worcester, Massachusetts

10. School of Biochemistry and Cell Biology, University College Cork, Cork, Ireland

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.

Funder

Science Foundation Ireland

Publisher

American Physiological Society

Subject

Physiology (medical),Gastroenterology,Hepatology,Physiology

Link

https://journals.physiology.org/doi/pdf/10.1152/ajpgi.00104.2022

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