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 - 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.
UR - https://www.scopus.com/pages/publications/85031699072
UR - https://www.scopus.com/pages/publications/85031699072#tab=citedBy
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 -
