For COVID-19 vaccine updates, please review our information guide. For patient eligibility and scheduling availability, please visit VaccineTogetherNY.org.

A Crohn's disease-associated NOD2 mutation suppresses transcription of human IL10 by inhibiting activity of the nuclear ribonucleoprotein hnRNP-A1.

TitleA Crohn's disease-associated NOD2 mutation suppresses transcription of human IL10 by inhibiting activity of the nuclear ribonucleoprotein hnRNP-A1.
Publication TypeJournal Article
Year of Publication2009
AuthorsNoguchi E, Homma Y, Kang X, Netea MG, Ma X
JournalNat Immunol
Volume10
Issue5
Pagination471-9
Date Published2009 May
ISSN1529-2916
KeywordsAdult, Animals, Crohn Disease, Female, Gene Expression Regulation, Genetic Predisposition to Disease, Heterogeneous Nuclear Ribonucleoprotein A1, Heterogeneous-Nuclear Ribonucleoprotein Group A-B, Humans, Interleukin-10, Macrophages, Male, Mice, Mice, Knockout, Monocytes, Mutation, Nod2 Signaling Adaptor Protein, Transcription, Genetic
Abstract

A common mutation in the gene encoding the cytoplasmic sensor Nod2, involving a frameshift insertion at nucleotide 3020 (3020insC), is strongly associated with Crohn's disease. How 3020insC contributes to this disease is a controversial issue. Clinical studies have identified defective production of interleukin 10 (IL-10) in patients with Crohn's disease who bear the 3020insC mutation, which suggests that 3020insC may be a loss-of-function mutation. However, here we found that 3020insC Nod2 mutant protein actively inhibited IL10 transcription. The 3020insC Nod2 mutant suppressed IL10 transcription by blocking phosphorylation of the nuclear ribonucleoprotein hnRNP-A1 via the mitogen-activated protein kinase p38. We confirmed impairment in phosphorylation of hnRNP-A1 and binding of hnRNP-A1 to the IL10 locus in peripheral blood mononuclear cells from patients with Crohn's disease who bear the 3020insC mutation and have lower production of IL-10.

DOI10.1038/ni.1722
Alternate JournalNat Immunol
PubMed ID19349988
PubMed Central IDPMC2928218
Grant ListR01 AI072149 / AI / NIAID NIH HHS / United States
R01 AI072149-01A2 / AI / NIAID NIH HHS / United States

Weill Cornell Medicine Microbiology and Immunology 1300 York Avenue, Box 62 New York, NY 10065 Phone: (212) 746-6505 Fax: (212) 746-8587