Excessive deubiquitination of NLRP3-R779C variant contributes to very-early-onset inflammatory bowel disease development

Lingli Zhou; Tao Liu; Bing Huang; Man Luo; Zhanghua Chen; Zhiyao Zhao; Jun Wang; Daniel Leung; Xingtian Yang; Koon Wing Chan; Yukun Liu; Liya Xiong; Peiyu Chen; Hongli Wang; Liping Ye; Hanquan Liang; Seth L Masters; Andrew M Lew; Sitang Gong; Fan Bai; Jing Yang; Pamela Pui-Wah Lee; Wanling Yang; Yan Zhang; Yu-Lung Lau; Lanlan Geng; Yuxia Zhang; Jun Cui

Journal article

Excessive deubiquitination of NLRP3-R779C variant contributes to very-early-onset inflammatory bowel disease development

Lingli Zhou, Tao Liu, Bing Huang, Man Luo, Zhanghua Chen, Zhiyao Zhao, Jun Wang, Daniel Leung, Xingtian Yang, Koon Wing Chan, Yukun Liu, Liya Xiong, Peiyu Chen, Hongli Wang, Liping Ye, Hanquan Liang, Seth L Masters, Andrew M Lew, Sitang Gong, Fan Bai Show all

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY | MOSBY-ELSEVIER | Published : 2021

DOI: 10.1016/j.jaci.2020.09.003

Abstract

BACKGROUND: Very-early-onset inflammatory bowel disease (VEOIBD) is a chronic inflammatory disease of the gastrointestinal tract occurring during infancy or early childhood. NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome has emerged as a crucial regulator of intestinal homeostasis; however, whether NLRP3 variants may modify VEOIBD risk is unknown. OBJECTIVE: We sought to investigate whether and how a rare NLRP3 variant, found in 3 patients with gastrointestinal symptoms, contributes to VEOIBD development. METHODS: Whole-exome sequencing and bioinformatic analysis were performed to screen disease-associated NLRP3 variants from a cohort of children with VEOIBD. Inflam..

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University of Melbourne Researchers

Andrew Lew Author Medical Biology (w.e.h.i.)

Seth Masters Author Medical Biology (w.e.h.i.)

Grants

Awarded by National Natural Science Foundation of China

Awarded by Society for the Relief of Disabled Children, Innovation and Technology Fund, Innovation and Technology Commission, the Government of the Hong Kong Special Administrative Region

Awarded by Fundamental Research Funds for the Central Universities

Awarded by National Health and Medical Research Council of Australia

Funding Acknowledgements

This work was supported by the National Natural Science Foundation of China (grant nos. 31870862, 31770978, 91742109, and 81873869), The Society for the Relief of Disabled Children, Innovation and Technology Fund, Innovation and TechnologyCommission, the Government of the Hong Kong Special Administrative Region (ITS/417/18), the Fundamental Research Funds for the Central Universities (19lgpy198), and the National Health andMedical Research Council ofAustralia (grant nos. 1143976, 1150425, and 1080321). S.L.M. acknowledges funding from The Sylvia and Charles Viertel Foundation and HHMI-Wellcome International Research Scholarship.