CCDC88B is required for pathogenesis of inflammatory bowel disease /631/250/347 /692/699/1503/257/1402 article

Nassima Fodil, Neda Moradin, Vicki Leung, Jean Frederic Olivier, Irena Radovanovic, Thiviya Jeyakumar, Manuel Flores Molina, Ashley McFarquhar, Romain Cayrol, Dominique Bozec, Naglaa H. Shoukry, Michiaki Kubo, Julia Dimitrieva, Edouard Louis, Emilie Theatre, Stephanie Dahan, Yukihide Momozawa, Michel Georges, Garabet Yeretssian, Philippe Gros

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6 Citations (Scopus)

Abstract

Inflammatory bowel disease (IBD) involves interaction between host genetic factors and environmental triggers. CCDC88B maps within one IBD risk locus on human chromosome 11q13. Here we show that CCDC88B protein increases in the colon during intestinal injury, concomitant with an influx of CCDC88B+lymphoid and myeloid cells. Loss of Ccdc88b protects against DSS-induced colitis, with fewer pathological lesions and reduced intestinal inflammation in Ccdc88b-deficient mice. In a T cell transfer model of colitis, Ccdc88b mutant CD4+ T cells do not induce colitis in immunocompromised hosts. Expression of human CCDC88B RNA and protein is higher in IBD patient colons than in control colon tissue. In human CD14+ myeloid cells, CCDC88B is regulated by cis-acting variants. In a cohort of patients with Crohn's disease, CCDC88B expression correlates positively with disease risk. These findings suggest that CCDC88B has a critical function in colon inflammation and the pathogenesis of IBD.

Original languageEnglish
Article number932
JournalNature communications
Volume8
Issue number1
DOIs
Publication statusPublished - 01-12-2017

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Fodil, N., Moradin, N., Leung, V., Olivier, J. F., Radovanovic, I., Jeyakumar, T., Flores Molina, M., McFarquhar, A., Cayrol, R., Bozec, D., Shoukry, N. H., Kubo, M., Dimitrieva, J., Louis, E., Theatre, E., Dahan, S., Momozawa, Y., Georges, M., Yeretssian, G., & Gros, P. (2017). CCDC88B is required for pathogenesis of inflammatory bowel disease /631/250/347 /692/699/1503/257/1402 article. Nature communications, 8(1), [932]. https://doi.org/10.1038/s41467-017-01381-y