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Nat Commun. 2017 Oct 13;8(1):932. doi: 10.1038/s41467-017-01381-y.

CCDC88B is required for pathogenesis of inflammatory bowel disease.

Author information

1
McGill Center for the Study of Complex Traits, Department of Human Genetics, Department of Biochemistry, McGill University, 3649 Sir William Osler Promenade, Montreal, QC, Canada, H3G 0B1. nassima.fodil@mcgill.ca.
2
McGill Center for the Study of Complex Traits, Department of Human Genetics, Department of Biochemistry, McGill University, 3649 Sir William Osler Promenade, Montreal, QC, Canada, H3G 0B1.
3
Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), 900, Saint Denis Street, Pavillion R, Montreal, QC, Canada, H20A9.
4
Département de Pathologie et de Biologie Cellulaire de l'Université de Montréal, C.P. 6128, succ. Centre-ville, Montréal, QC, Canada, H3C 3J7.
5
Immunology Institute, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
6
Laboratory for Genotyping Development, Center for Integrative Medical Sciences, RIKEN 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan.
7
Unit of Animal Genomics, GIGA-R and Faculty of Veterinary Medicine, Universite de Liège (B34), avenue de l'Hôpital 1, 4000, Liège, Belgium.
8
SOBI, Inc, Waltham, MA, 02452, USA.
9
The Leona M. and Harry B. Helmsley Charitable Trust, New York, NY, 10169, USA.
10
McGill Center for the Study of Complex Traits, Department of Human Genetics, Department of Biochemistry, McGill University, 3649 Sir William Osler Promenade, Montreal, QC, Canada, H3G 0B1. philippe.gros@mcgill.ca.

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.Hook-related protein family member CCDC88b is encoded by a locus that has been associated with inflammatory bowel disease. Here the authors show that Ccdc88b inactivation in T cells prevents colitis in a transfer model, and detect high colonic levels of CCDC88b in patients with Crohn disease or ulcerative colitis, identifying that expression correlates with disease risk.

PMID:
29030607
PMCID:
PMC5640600
DOI:
10.1038/s41467-017-01381-y
[Indexed for MEDLINE]
Free PMC Article
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