气候变化领域集成服务门户(CCPortal): Homozygous IL37 mutation associated with infantile inflammatory bowel disease

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DOI	10.1073/pnas.2009217118
	Homozygous IL37 mutation associated with infantile inflammatory bowel disease
	Zhang Z.Z.; Zhang Y.; He T.; Sweeney C.L.; Baris S.; Karakoc-Aydiner E.; Yao Y.; Ertem D.; Matthews H.F.; Gonzaga-Jauregui C.; Malech H.L.; Su H.C.; Ozen A.; Smith K.G.C.; Lenardo M.J.
发表日期	2021
ISSN	00278424
卷号	118 期号:10
英文摘要	Interleukin (IL)-37, an antiinflammatory IL-1 family cytokine, is a key suppressor of innate immunity. IL-37 signaling requires the heterodimeric IL-18R1 and IL-1R8 receptor, which is abundantly expressed in the gastrointestinal tract. Here we report a 4-mo-old male from a consanguineous family with a homozygous loss-of-function IL37 mutation. The patient presented with persistent diarrhea and was found to have infantile inflammatory bowel disease (I-IBD). Patient cells showed increased intracellular IL-37 expression and increased proinflammatory cytokine production. In cell lines, mutant IL-37 was not stably expressed or properly secreted and was thus unable to functionally suppress proinflammatory cytokine expression. Furthermore, induced pluripotent stem cell–derived macrophages from the patient revealed an activated macrophage phenotype, which is more prone to lipopolysaccharide and IL-1β stimulation, resulting in hyperinflammatory tumor necrosis factor production. Insights from this patient will not only shed light on monogenic contributions of I-IBD but may also reveal the significance of the IL-18 and IL-37 axis in colonic homeostasis. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	IBD; IL37; Immunodeficiency; Inflammatory bowel disease; VEO-IBD
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180411
作者单位	National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, United States; Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge, CB2 0AW, United Kingdom; School of Medicine, Marmara University, Istanbul, 34722, Turkey; Regeneron Genetics Center, Tarrytown, NY 10591, United States
推荐引用方式 GB/T 7714	Zhang Z.Z.,Zhang Y.,He T.,et al. Homozygous IL37 mutation associated with infantile inflammatory bowel disease[J],2021,118(10).
APA	Zhang Z.Z..,Zhang Y..,He T..,Sweeney C.L..,Baris S..,...&Lenardo M.J..(2021).Homozygous IL37 mutation associated with infantile inflammatory bowel disease.Proceedings of the National Academy of Sciences of the United States of America,118(10).
MLA	Zhang Z.Z.,et al."Homozygous IL37 mutation associated with infantile inflammatory bowel disease".Proceedings of the National Academy of Sciences of the United States of America 118.10(2021).