TY - JOUR
T1 - CCDC88B is required for pathogenesis of inflammatory bowel disease /631/250/347 /692/699/1503/257/1402 article
AU - Fodil, Nassima
AU - Moradin, Neda
AU - Leung, Vicki
AU - Olivier, Jean Frederic
AU - Radovanovic, Irena
AU - Jeyakumar, Thiviya
AU - Flores Molina, Manuel
AU - McFarquhar, Ashley
AU - Cayrol, Romain
AU - Bozec, Dominique
AU - Shoukry, Naglaa H.
AU - Kubo, Michiaki
AU - Dimitrieva, Julia
AU - Louis, Edouard
AU - Theatre, Emilie
AU - Dahan, Stephanie
AU - Momozawa, Yukihide
AU - Georges, Michel
AU - Yeretssian, Garabet
AU - Gros, Philippe
N1 - Funding Information:
This work was supported by research grants to PG from the Canadian Institutes of Health Research; grants from WELBIO (Grant CAUSIBD) and from BELSPO (PAI BeMGI) for M.G., E.T., Y.M., J.D. and E.D. Work in the Shoukry lab was supported by pilot project funding from Fonds de Recherche du Québec–Santé (FRQS) AIDS and Infectious Disease Network (Réseau SIDA-MI) and the Canadian Network on Hepatitis C (CanHepC). MFM received fellowships from the Université de Montréal, Bourse Gabriel Marquis and the FRQS. NHS is supported by a Chercheur Boursier salary award from the FRQS. G.Y.’s work at Mount Sinai was supported by The Leona M. and Harry B. Helmsley Charitable Trust. We thank Dr. Petronela Ancuta (Universite de Montreal) for sharing reagents. We thank Maryse Dagenais, Alexandre Morizot, and Claudia Champagne (McGill University) for technical help. The authors are indebted to Genevieve Perreault for expert technical assistance. S.D. is currently is employed by Sobi, Inc.; the article in no way represents the work product, views or opinions of Sobi, Inc. G.Y. is currently employed by The Leona M. and Harry B. Helmsley Charitable Trust; the article in no way represents the work, views or opinions of Helmsley.
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-017-01381-y
DO - 10.1038/s41467-017-01381-y
M3 - Article
C2 - 29030607
AN - SCOPUS:85031699072
SN - 2041-1723
VL - 8
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 932
ER -